Biomedical subjects

S Nakamura

Publications and source records attributed to S Nakamura.

At least 19 recordsLinked to original sources

PubMed2006

Reverse white-coat effect as an independent risk for left ventricular concentric hypertrophy in patients with treated essential hypertension.

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBP > or =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBP<daytime SBP, n=123). LV mass index and relative wall thickness were echocardiographically determined. In all subjects, LV mass index and relative wall thickness were positively correlated with daytime and 24-h SBP, but not with office SBP. In addition, these two indices were inversely correlated with office--daytime SBP difference. LV mass index (136+/-31 and 115+/-28 g/m(2), mean+/-s.d.) and relative wall thickness (0.49+/-0.09 and 0.46+/-0.07) were significantly greater in Group 2 than in Group 1. As for LV geometric patterns, Group 2 had a significantly higher rate of concentric hypertrophy compared with Group 1 (48 and 28%). Multivariate analyses revealed that the presence of reverse white-coat effect was a predictor for LV concentric hypertrophy, independent of age, sex, hypertension duration, antihypertensive treatment and ambulatory blood pressure levels. Our findings demonstrate that reverse white-coat effect is an independent risk factor for LV hypertrophy, especially concentric hypertrophy, in treated hypertensive patients.

Aged↗

PubMed2006

Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patients.

Lymphadenopathy, which may be associated with systemic symptoms, is frequently associated with rheumatoid arthritis (RA). Reactive non-neoplastic tissue comprises the majority of the lymph node lesions. However, several cohort studies have demonstrated that RA has an increased risk of non-Hodgkin's lymphomas (NHLs). Since the early 1990s, an atypical or malignant lymphoproliferative disorders (LPD) in patients immunosupressed with methtorexate (MTX) therapy for RA has been emphasized, namely MTX-associated LPDs. Epstein-Barr virus (EBV) has received attention in connection with the etiology of RA. The present review describes the clinicopathologic and immunohistochemical findings of reactive, atypical and malignant LPDs associated with RA along with the presence or absence of EBV in LPDs using the in situ hybridization (ISH) method. The majority of reactive lymph node lesions exhibit reactive follicular hyperplasia with interfollicular polyclonal plasmacytosis. Atypical LPDs rarely appears in RA patients. However, these cases occasionally pose difficult problems in the differential diagnosis from malignant lymphomas associated with RA or atypical and malignant LPDs showing RA-like clinicopathological findings. Clinicopathologically, three types of atypical LPDs have delineated, i.e. (i) resembling multicentric Castleman's disease (MCD); (ii) atypical paracortical hyperplasia with lymphoid follicles (APHLF) and; (iii) atypical lymphoplasmacytic immunoblastic proliferation. Malignant lymphoma associated with RA is characterized by; (i) predominance of elderly cases; (ii) usually female predominance, reflecting the sex ratio of RA; (iii) longstanding history of RA; (iv) relatively frequent advanced stage of disease; (v) majority of the patients had the B-cell phenotype; and (vi) an increased frequency of diffuse large B-cell lymphoma (DLBCL) in RA. It is unlikely that EBV is the causative agent of either reactive or atypical LPD. Among malignant lymphomas, EBV-associated lymphoma comprised only a small fraction of all NHLs in the general RA patient population.

Arthritis, Rheumatoid↗

PubMed2006

Clinicopathological features of pyothorax-associated lymphoma; a retrospective survey involving 98 patients.

To investigate clinicopathological features of pyothorax-associated lymphoma (PAL), we examined medical records of 98 patients (88 males and 10 females) with PAL at a median age of 70 years (range 51-86). Seventy-nine patients had a history of artificial pneumothorax. Median interval between diagnosis and artificial pneumothorax was 43 years (range 19-64). At diagnosis, performance status (PS) was 0-1 (n=56) and 2-4 (n=42). Clinical stages were I (n=42), II (n=26), III (n=8) and IV (n=22). Pathological diagnosis comprised diffuse large-B-cell (n=78) and peripheral T-cell lymphoma (n=1). Seventeen were treated supportively. The other 81 received aggressive treatments; chemotherapy (n=52), radiotherapy (n=7), surgery (n=4) and combination (n=18). Five-year overall survival (OS) was 0.35 (95% confidence interval, 24% to 45%). Causes of deaths were PAL (n=39), respiratory failure (n=13) and others (n=12). Multivariate analysis identified prognostic factors for OS; lactate dehydrogenase levels [hazard ratio (HR)=2.36; P=0.013], sex (female versus male) (HR=0.15; P=0.01), PS (2-4 versus 0-1) (HR=2.20; P=0.02), clinical stages (III/IV versus I/II) (HR=1.95; P=0.037) and chemotherapy (HR=0.31; P=0.01). Most patients with PAL are elderly and have comorbidities, while some of them achieve durable remission with appropriate treatments. These findings prompt us to establish an optimal treatment strategy on the basis of risk stratification of individual patients.

Aged↗

PubMed2006

Complete elimination of maternal mitochondrial DNA during meiosis resulting in the paternal inheritance of the mitochondrial genome in Chlamydomonas species.

The non-Mendelian inheritance of organellar DNA is common in most plants and animals. In the isogamous green alga Chlamydomonas species, progeny inherit chloroplast genes from the maternal parent, as paternal chloroplast genes are selectively eliminated in young zygotes. Mitochondrial genes are inherited from the paternal parent. Analogically, maternal mitochondrial DNA (mtDNA) is thought to be selectively eliminated. Nevertheless, it is unclear when this selective elimination occurs. Here, we examined the behaviors of maternal and paternal mtDNAs by various methods during the period between the beginning of zygote formation and zoospore formation. First, we observed the behavior of the organelle nucleoids of living cells by specifically staining DNA with the fluorochrome SYBR Green I and staining mitochondria with 3,3'-dihexyloxacarbocyanine iodide. We also examined the fate of mtDNA of male and female parental origin by real-time PCR, nested PCR with single zygotes, and fluorescence in situ hybridization analysis. The mtDNA of maternal origin was completely eliminated before the first cell nuclear division, probably just before mtDNA synthesis, during meiosis. Therefore, the progeny inherit the remaining paternal mtDNA. We suggest that the complete elimination of maternal mtDNA during meiosis is the primary cause of paternal mitochondrial inheritance.

Animals↗

PubMed2006

Thalidomide reduces IL-18, IL-8 and TNF-alpha release from alveolar macrophages in interstitial lung disease.

Thalidomide exhibits diverse actions of anti-inflammation, immunomodulation and anti-angiogenesis. The efficacy of thalidomide treatment in sarcoidosis with lupus pernio is thought to be due to inhibition of tumour necrosis factor (TNF)-alpha. The mechanisms that underlie the properties of thalidomide are still unclear in interstitial lung disease. The current authors investigated the potential inhibitory effects of thalidomide at concentrations of 0.1, 0.01 and 0.001 mM on the production of transforming growth factor-beta, TNF-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, IL-12p40 and IL-18 by alveolar macrophages from bronchoalveolar lavage in patients with sarcoidosis (n = 8), hypersensitivity pneumonitis (HP; n = 8) and idiopathic pulmonary fibrosis (IPF; n = 12). In sarcoidosis and HP patients, thalidomide induced a dose-dependent, partial suppression of lipopolysacchride (LPS)-stimulated TNF-alpha, IL-12p40 and IL-18 release. At the highest thalidomide concentration (0.1 mM), LPS-stimulated IL-8 production was also suppressed. In IPF patients, although spontaneous production of TNF-alpha, IL-12p40, IL-18 and IL-8 was lower than in sarcoidosis and HP patients, with LPS stimulation the cytokines were significantly elevated and also partially inhibited by thalidomide. In conclusion, thalidomide has the potential to improve the therapeutic regimens for sarcoidosis, hypersensitivity pneumonitis and idiopathic pulmonary fibrosis by reducing tumour necrosis factor-alpha, interleukin-12p40, interleukin-18 and interleukin-8 production.

Aged↗

PubMed2006

Comparison of the transcutaneous oxygen and carbon dioxide tension in different electrode locations during general anaesthesia.

BACKGROUND AND OBJECTIVE: The best place for the electrode of transcutaneous measurement of oxygen tension (tcPO2) and carbon dioxide tension (tcPCO2) during general anaesthesia was investigated in three different locations. METHODS: Fifteen patients for major abdominal surgery in the supine position were studied. The electrode of the TCM4 (Radiometer, Copenhagen, Denmark) was put on the chest, upper arm or forearm. TcPO2, tcPCO2, end-tidal carbon dioxide tension (etCO2), percutaneous oxygen saturation (SaO2), arterial oxygen tension (PaO2 ) and arterial carbon dioxide tension (PaCO2) were simultaneously measured at four different etCO2 concentrations and inhaled oxygen percentages and the location of the electrode was changed to other places to repeat the same measurement. In total, 12 measurements for each patient and 60 measurements for each place were performed. RESULTS: TcPO2 correlated better than SaO2 (R2 = 0.58) with PaO2 (R2 = 0.76), and tcPCO2 correlated well with PaCO2 (R2 = 0.76) and etCO2 (R2 = 0.74) when the electrode was put on the chest, while not on the upper arm or forearm (R2 < 0.5). However, limits of agreement were too big to use tcPO2 (bias, -67.9; limits of agreement, 16.5, -152.3) and tcPCO2 (bias, -0.47; limits of agreement, 8.7, -9.64) as surrogate measures of PaO2 and PaCO2, respectively even when the electrode was put on the chest. CONCLUSIONS: When the electrode was put on the chest, tcPO2 and tcPCO2 might be available as non-invasive monitors of oxygenation and CO2 status during general anaesthesia, while the absolute values were not interchangeable with PaO2 and PaCO2, respectively.

Aged↗

PubMed2006

Instructive role of a peripheral pattern for the central patterning of the trigeminal projection at the brainstem and thalamus revealed by an artificially altered whisker pattern.

The central patterning mechanism of neuronal circuits is an important issue in developmental neuroscience. We report here the role of a peripheral whisker pattern for the patterning of the trigeminal projection at the brainstem and thalamus in the mouse somatosensory system. The whisker pattern was manipulated by infecting the embryonic epidermis with adenovirus harboring Shh. The ectopic expression of Shh led to the induction of extra whiskers and displacement of whiskers, where these whiskers were histologically normal. The altered whisker pattern was isomorphically represented in the brainstem (barrelette: subnuclei principalis and subnuclei interpolaris), thalamus (barreloid) and cortex (barrel) as revealed by cytochrome oxidase staining. The barrelette-like pattern of the parvalbumin became discernible by immunostaining at P7 in subnuclei principalis and at P4 in subnuclei interpolaris in normal mice. These are the barrelette neurons projecting to the thalamus and the local circuit within the barrelette. The barrelette-like parvalbumin pattern also exhibits the altered whisker pattern induced by the adenovirus harboring Shh. These results highlight the role the peripheral whisker pattern for the central patterning of the brainstem, thalamus, and cortex in the mouse somatosensory system.

Adenoviridae↗

PubMed2006

Differential effects of prenatal stress on the morphological maturation of hippocampal neurons.

The present study was designed to clarify an intensity-dependent effect of prenatal stress on the morphological development of hippocampal neurons in rats. In addition, the involvement of receptors for glucocorticoids, i.e. mineralocorticoid receptors and glucocorticoid receptors, in stress-induced changes in the morphology of hippocampal neurons was examined by an in vitro pharmacological approach. The effects of mild prenatal stress on neurogenesis and long-term potentiation in the hippocampus were also investigated in adult offspring. Prenatal stress affected the morphological development of the hippocampus in an intensity-dependent manner. Short-lasting, mild prenatal stress enhanced neonatal neurogenesis and differentiation of processes of hippocampal neurons, whereas long-lasting, severe stress impaired their morphology. Mineralocorticoid receptor was found to mediate enhancement of neurogenesis and differentiation of processes of cultured hippocampal neurons. In contrast, glucocorticoid receptor was involved in the suppression of their morphology. Short-lasting, mild prenatal stress, which has previously been shown to enhance learning performance in adult offspring, facilitated neurogenesis and long-term potentiation in the adult hippocampus. These findings suggest that prenatal stress has enhancing and suppressing effects on the development of hippocampal neurons depending on intensity, and that mineralocorticoid receptors and glucocorticoid receptors contribute to stress-induced morphological changes.

Animals↗

PubMed2006

Development of GABA-sensitive spasticity and rigidity in rats after transient spinal cord ischemia: a qualitative and quantitative electrophysiological and histopathological study.

Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor evoked potentials. In addition the effect of intrathecal treatment with baclofen (GABAB receptor agonist; 1 microg), nipecotic acid (GABA uptake inhibitor; 300 microg) and dorsal L2-L5 rhizotomy on spasticity and rigidity was studied. Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized using immunofluorescence and confocal microscopy. At 3-7 days after ischemia an increase in tonic electromyographic activity with a variable degree of rigidity was seen. In animals with modest rigidity a velocity-dependent increase in muscle resistance and corresponding appearance in electromyographic activity (consistent with the presence of spasticity) was measured during ankle rotation (4-612 degrees /s rotation). Measurement of the H-reflex revealed a significant increase in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the same animals a potent increase in motor evoked potential amplitudes was measured and this change correlated positively with the increased H-reflex responses. Spasticity and rigidity were consistently present for a minimum of 3 months after ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and nipecotic acid (GABA uptake inhibitor) provided a significant suppression of spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2-L5 rhizotomy significantly decreased muscle resistance but had no effect on increased amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII. These data demonstrate that brief transient spinal cord ischemia in rat leads to a consistent development of spasticity and rigidity. The lack of significant suppressive effect of dorsal L2-L5 rhizotomy on motor evoked potentials response indicates that descending motor input into alpha-motoneurons is independent on Ia afferent couplings and can independently contribute to increased alpha-motoneuronal excitability. The pharmacology of this effect emphasizes the potent role of GABAergic type B receptors in regulating both the spasticity and rigidity.

Acetyltransferases↗

PubMed2006

Comparative study on mechanoluminescence of irradiated and non-irradiated ionic crystals.

Effect of surrounding gas on mechanoluminescence (ML) of non-irradiated KCl:Ca2+ and X-ray irradiated one has been investigated in order to clarify the ML due to dislocation movement. For both samples, the ML appears only in the narrow pressure range from 10 to 10(3) Pa with a peak at 133 Pa. Emission spectrum of ML for both samples in Ne gas has indicated a prominent peak at 580 nm that coincides with a strong line of Ne gas. Above results indicate that the observed ML is caused by electric discharge at the crystal surface. Discussion is also made on the effect of Ca2+ on both the ML intensity and the charges carried with dislocations.

Computer Simulation↗

PubMed2006

Blood vessel density correlates with the effects of targeted intra-arterial carboplatin infusion with concurrent radiotherapy for squamous cell carcinomas of the oral cavity and oropharynx.

Our aim was first to evaluate the association between blood vessel density (BVD) and free platinum concentration in experimentally induced tumours in rabbits. We also investigated the association between tumour BVD and the clinical response of patients who had undergone targeted carboplatin intra-arterial (i.a.) chemoradiotherapy. VX2 carcinoma cells were transplanted into 46 inbred female Japanese white rabbits. In the i.a. group, carboplatin was infused into the lingual artery, and in the intravenous (i.v.) group, carboplatin was infused through the auricular vein. In the clinical study, we evaluated 19 patients with squamous cell carcinomas of the oral cavity and oropharynx, who had undergone targeted carboplatin i.a. chemoradiotherapy and had been administered i.a. tegafur/uracil chemotherapy before surgery. We quantified angiogenesis in both studies. Increased BVD was associated with a higher free platinum concentration in the tumour region in the i.a. group of rabbits. In the clinical study, using multivariate logistic regression analysis, only the BVD was related independently to the treatment effect. Therefore, BVD is a valid predictor of the effects of i.a. targeted carboplatin chemotherapy and concurrent radiotherapy for treating human oral and oropharyngeal squamous cell carcinomas.

Animals↗

PubMed2006

Effect of electrical polarization of hydroxyapatite ceramics on new bone formation.

Large surface charges can be induced on hydroxyapatite (HAp) ceramics by proton transport polarization, but this does not affect beta-tricalcium phosphate (TCP) because of its low polarizability. We wished to examine differences in osteogenic cell activity and new bone growth between positively or negatively surface-charged HAp and HAp/TCP plates using a calvarial bone defect model. In the first group of rats, test pieces were placed with their positively charged surfaces face down on the dura mater. In the second group, test pieces were placed with their negatively charged surfaces face down on the dura mater. A third group received noncharged test pieces. Histological examination, including enzymatic staining for osteoblasts and osteoclasts, was carried out. While no bone formation was observed at the pericranium, direct bone formation on the cranial bone debris and new bone growth expanded from the margins of the sites of injury to bridge across both the positively and negatively charged surfaces of HAp and HAp/TCP plates occurred. Electrical polarization of implanted plates, including positive charge, led to enhanced osteoblast activity, though decreased osteoclast activity was seen on the positively charged plate surface. Thus, polarization of HAp ceramics may modulate new bone formation and resorption.

Animals↗

PubMed2006

Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

Journal Article↗

PubMed2006

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines.

AIM: To ascertain whether vitreous and plasma levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and fundus findings could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid samples were obtained during vitreoretinal surgery from 73 consecutive eyes with PDR. The levels of VEGF and IL-6 in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. RESULTS: No improvement and/or progression of PDR occurred in 23 (32%) of the 73 eyes (progression group). The vitreous levels of VEGF and IL-6 were significantly higher in eyes from the progression group than in eyes with regression of PDR (regression group) (P=0.0032 and 0.0088, respectively). Multivariate logistic regression analysis showed that higher vitreous levels of VEGF were associated with the progression of PDR after vitreous surgery (odds ratio 2.72, P=0.0003). CONCLUSIONS: High vitreous levels of VEGF identified as a significant risk factor for the outcome of vitreous surgery in patients with PDR. A model was developed to predict the probability of PDR progression and measurement of the vitreous level of VEGF may be useful for predicting the outcome of surgery.

Adult↗

PubMed2006

Improvement in motion efficiency of the spirochete Brachyspira pilosicoli in viscous environments.

Spirochetes are unique among swimming bacteria in terms of their lack of external flagella. They actively move in viscous environments, and, surprisingly, the swimming speed of the spirochete Leptospira interrogans has been reported to increase with viscosity in methylcellulose solutions. Many researchers consider that the presence of a loose, quasi-rigid network formed by linear polymer molecules is related to this strange phenomenon. One of the authors has proposed a theory that expresses this idea mathematically and successfully explains the speed properties of an externally flagellated bacterium in viscous environments. This theory predicts that the ratio of swimming speed to wave frequency (v/f ratio, motion efficiency in a sense) increases with viscosity. In this study, we demonstrated a new method of measuring the swimming speed and wave frequency of spirochetes and the motion characteristics of a swine intestinal spirochete, Brachyspira pilosicoli strain NK1f, measured in viscous environments. Several sets of swimming speed and wave frequency data were simultaneously derived from an animation obtained by our method. The v/f ratio of NK1f displayed a tendency to increase with increasing viscosity, suggesting the validity of the above-mentioned theory. Improvement of motion efficiency is at least one of the factors that maintain spirochete motility in viscous environments.

Animals↗

PubMed2006

Estimation of photon dose generated by a short pulse high power laser.

The authors obtain a new equation to estimate the forward component of a photon dose generated through the interaction between a target and a short pulse high power laser. As the equation is quite simple, it is useful for calculating the photon dose. The equation shows that the photon dose is proportional to the electron temperature in the range>3 MeV and proportional to the square of the electron temperature in the range<3 MeV. The dose estimated with this method is roughly consistent with the result of Monte Carlo simulation. With some assumptions and corrections, it can reproduce experimental results obtained and the dose result calculated at other laboratories.

Electrons↗

PubMed2006

Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms.

Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.

Adolescent↗

PubMed2006

N2-carboxyethyl-2'-deoxyguanosine, a DNA glycation marker, in kidneys and aortas of diabetic and uremic patients.

Advanced glycation end product (AGE)-mediated modification of proteins is enhanced both in the kidneys and aortas of diabetic and uremic patients. However, AGE modification of deoxyribonucleic acid (DNA) has not yet been reported in these patients. We performed immunohistochemistry of kidneys and aortas using a monoclonal antibody against N(2)-carboxyethyl-2'-deoxyguanosine (CEdG), a marker of AGE-linked DNA. A total of 20 kidneys and 20 aortas were obtained by autopsy. The kidney samples consisted of two groups: nondiabetic nonkidney disease (control) and diabetic nephropathy. The aorta samples consisted of four groups: nondiabetic nonkidney disease (control), diabetes, hemodialysis, and diabetic hemodialysis. In the kidneys CEdG was detected predominantly in the nuclei of epithelial cells, mesangial cells, and endothelial cells of the glomeruli, parietal epithelial cells, and tubular cells. The number of CEdG-positive cells in the glomeruli was significantly increased in diabetic nephropathy compared with control. In the aortic walls, CEdG was detected predominantly in the nuclei of macrophages and myofibroblasts. The number of CEdG-positive cells in the aorta was significantly increased in hemodialysis patients and diabetic hemodialysis patients compared with control. The highest number of CEdG-positive cells in the aorta was observed in diabetic hemodialysis patients. In conclusion, AGE-mediated modification of DNA is enhanced in the kidney of diabetic nephropathy and the aorta of uremic atherosclerosis, and may induce a loss of genetic integrity in these diseases.

Adult↗