LET Dependence of 8-Hydroxy-2'-deoxyguanosine (8-OHdG) Generation in Mammalian Cells under Air-Saturated and Hypoxic Conditions: A Possible Experimental Approach to the Mechanism of the Decreasing Oxygen Effect in the High-LET Region.

One of the most distinguished features in biological effects of heavy ions would be the decrease of oxygen effect in the high-LET region. This feature has been referred to as the radiobiological basis for the control of hypoxic fraction in cancer radiotherapy. However, mechanisms to explain this phenomenon have not been fully understood. One of the explanations was given by the oxygen in the track hypothesis, which proposes that oxygen is produced along ion tracks even in the hypoxic irradiation condition. In the present study, we designed an experimental approach to support this hypothesis by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as DNA damage requiring oxygen to produce. The LET dependence of 8-OHdG under hypoxic condition revealed that with increasing LET 8-OHdG yield seems to increase, despite that the yield of OH radical, which is also required for the production of 8-OHdG, decreases in the high-LET region. This result is consistent with the explanation that the local generation of oxygen along ion tracks contributes to the increase of 8-OHdG yield.

Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma.

The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly (P<0.00001). An ACD4C<343 × 106/l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 106/l (73.7% (95% confidence interval (CI)=66.7-79.5) versus 50.3% (95% CI=39.0-60.6), P<0.00001 and 83.3% (95% CI=77.1-88.0) versus 59.0% (95% CI=47.9-68.5), P<0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3-3.7), P<0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.

Optical diagnostics of a gliding arc.

Dynamic processes in a gliding arc plasma generated between two diverging electrodes in ambient air driven by 31.25 kHz AC voltage were investigated using spatially and temporally resolved optical techniques. The life cycles of the gliding arc were tracked in fast movies using a high-speed camera with framing rates of tens to hundreds of kHz, showing details of ignition, motion, pulsation, short-cutting, and extinction of the plasma column. The ignition of a new discharge occurs before the extinction of the previous discharge. The developed, moving plasma column often short-cuts its current path triggered by Townsend breakdown between the two legs of the gliding arc. The emission from the plasma column is shown to pulsate at a frequency of 62.5 kHz, i.e., twice the frequency of the AC power supply. Optical emission spectra of the plasma radiation show the presence of excited N2, NO and OH radicals generated in the plasma and the dependence of their relative intensities on both the distance relative to the electrodes and the phase of the driving AC power. Planar laser-induced fluorescence of the ground-state OH radicals shows high intensity outside the plasma column rather than in the center suggesting that ground-state OH is not formed in the plasma column but in its vicinity.

Associations of vertebral deformities and osteoarthritis with back pain among Japanese women: the Hizen-Oshima study.

UNLABELLED: We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain. INTRODUCTION: Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan. METHODS: Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren-Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain. RESULTS: Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5-6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0--0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1-2.9), independent of other covariates including age and deformities. CONCLUSION: Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.

SU-E-T-240: Accuracy of Dose Attenuation Correction for a 6D Carbon Fiber Treatment Couch Using a Virtual Couch Technique Integrated into a Treatment Planning System.

PURPOSE: A commercial 6D carbon fiber radiotherapy treatment couch (Imaging Couch Top, BrainLAB) has recently been reported to attenuate photon beams and increase skin dose. To prevent skin toxicity and ensure the target dose, it is important to correct the attenuation properties of the treatment couch with the treatment planning system (TPS). In this study, we evaluated the accuracy of dose attenuation correction by a virtual couch technique integrated into the TPS. METHODS: A virtual couch was modeled in the TPS (Eclipse v10.0, Varian). The CT value of the virtual couch was assigned with the CT value of the kilovoltage-CT images of the treatment couch. A phantom consisting of several plastic water slabs was created. We selected an evaluation point within the phantom on the couch structure at a 9 cm depth from the couch surface, which was placed at the isocenter. The doses at this point were calculated and measured at several gantry angles, from 120 degree to 240 degree at 10 degree steps, and each field size was 10 cm × 10 cm. The prescribed dose was 100 monitor units for 6/10 MV photon beams and 6 MV-SRS mode (Trilogy Tx, Varian). Dose measurements were performed with an ion chamber. RESULTS: The largest difference between measured and calculated doses was 3.3% for a gantry angle of 120 degree and 6 MV-SRS mode. The average dose difference was within 1.6% for all gantry angles and photon beams. In the case without attenuation correction, the largest difference was 8.2% and the average difference was 5.2%. CONCLUSIONS: Use of the virtual couch technique in TPS accomplished sufficient accuracy for dose attenuation correction of the 6D carbon fiber treatment couch, and it is an effective method for clinical use.

Skin autofluorescence is associated with severity of vascular complications in Japanese patients with Type 2 diabetes.

AIMS: Skin autofluorescence, a non-invasive measure of the accumulation for advanced glycation end products, has been reported to be a useful marker for diabetic vascular risks in the Caucasian population. The aim of this study was to evaluate associations between skin autofluorescence and vascular complications in non-Caucasian patients with Type 2 diabetes. METHODS: Subjects in this cross-sectional study comprised 130 Japanese patients with Type 2 diabetes. Skin advanced glycation end products were assessed by skin autofluorescence using an autofluorescence reader. Association between skin autofluorescence and severity of vascular complications was evaluated. RESULTS: Of the 130 patients, 60 (46.2%) had microvascular complications such as diabetic retinopathy, neuropathy and nephropathy, 10 (7.7%) had macrovascular complications and 63 (48.5%) had micro- and/or macrovascular complications. Skin autofluorescence increased with severity of vascular complications. Independent determinants of skin autofluorescence were age (ß = 0.24, P < 0.01), mean HbA(1c) in previous year (ß = 0.17, P = 0.03), microvascular complications (ß = 0.44, P < 0.01) and macrovascular complications (ß = 0.27, P < 0.01). Multiple logistic regression analysis revealed that diabetes duration (odds ratio 1.15, P < 0.01), systolic blood pressure (odds ratio 1.04, P = 0.01), skin autofluorescence (odds ratio 3.62, P = 0.01) and serum albumin (odds ratio 0.84, P < 0.01) were independent factors for the presence of vascular complications in these patients. CONCLUSIONS: Skin autofluorescence had independent effects on vascular complications in Japanese patients with Type 2 diabetes. This indicates that skin advanced glycation end products are a surrogate marker for vascular risk and a non-invasive autofluorescence reader may be a useful tool to detect high-risk cases in non-Caucasian patients with diabetes.

Quantitative ultrasound and radiographic absorptiometry are associated with vertebral deformity in Japanese Women: the Hizen-Oshima study.

UNLABELLED: We evaluated the ability of heel quantitative ultrasound (QUS) and metacarpal radiographic absorptiometry (RA) to identify subjects with vertebral deformities in Japanese women aged ≥40. Both QUS and RA were associated with vertebral deformities, and the estimated prevalence at each T-score widely varied with age. INTRODUCTION: Heel QUS and metacarpal RA have been used for screening patients to evaluate risk of osteoporotic fractures. The aim of this study was to evaluate the ability of QUS and RA to identify women with vertebral deformities in 570 Japanese women aged ≥40, and to estimate the prevalence of vertebral deformity at each T-score. METHODS: Calcaneal QUS and metacarpal RA were performed. Radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. RESULTS: The receiver operating characteristic analysis showed that both calcaneal stiffness index (SI) and metacarpal bone mineral density (BMD) were associated with vertebral deformities. Using the T-score of -2.5 as a cutoff value, the specificity and sensitivity for identifying individuals with vertebral deformities was 65% and 83% for calcaneal SI, and 40% and 88% for metacarpal BMD, respectively. The prevalence of vertebral deformity was estimated using age-adjusted logistic regression models. Women with calcaneal SI T-score of -2.5 had a 2% estimated probability of vertebral deformity at age 40, and 22% at age 80. For metacarpal BMD T-score of -2.5, estimated probability was less than 1% at age 40, and 27% at age 80. CONCLUSION: Both calcaneal SI and metacarpal BMD were associated with prevalence of vertebral deformity. Furthermore, the prevalence widely varied with age at any given bone value.

Prediction of functional outcome in acute cerebral hemorrhage using diffusion tensor imaging at 3T: a prospective study.

BACKGROUND AND PURPOSE: Early evaluation of the pyramidal tract is a prerequisite in patients with intracerebral hemorrhage (ICH) in order to decide the optimal treatment or to assess appropriate rehabilitation. The aim of this study was to evaluate and predict the neuromotor and functional outcome of an ICH by using diffusion tensor imaging (DTI) in the acute phase. MATERIALS AND METHODS: Eighteen patients with a hemiparetic supratentorial ICH were prospectively studied with DTI within 2 days after onset. A region-of-interest-based analysis was performed for the fractional anisotropy (FA) of the pyramidal tract in the cerebral peduncles. The degree of paresis was assessed at day 0 and day 28 by paresis grading (PG). The functional outcome was evaluated by the modified Rankin Scale (mRS). RESULTS: The FA in the affected side was significantly lower compared with that of the unaffected side (P = .001) with the mean diffusivity remaining unchanged (P = .50). The ratio of the FA (rFA) in the affected side to the unaffected side was significantly correlated with the PG at day 0 and 28 and the mRS score at day 28 (P = .002, r = -0.674; P < .001, r = -0.767; and P = .002, r = -0.676). The rFA for the good and poor outcomes based on the PG was significantly different (P < .001). The cutoff point of the rFA for the good and poor outcomes was set at 0.85 (sensitivity, 100%, specificity, 100%). CONCLUSIONS: We conclude that DTI can evaluate the motor deficit quantitatively and may predict the functional outcome in patients with an ICH who were scanned within 2 days after the ICH onset.

[Prevalence of disabilities of the upper and lower extremities among community-dwelling middle-aged and elderly women].

OBJECTIVE: In order to obtain baseline data for designing programs aimed at promoting physical function among elderly people in Japan, we determined the prevalence of disabilities affecting upper and lower extremities and their impact on function in community-dwelling middle-aged and elderly Japanese women. METHODS: Subjects were 580 women aged 40 years and over, living in Oshima town, Nagasaki, Japan. Information on disabilities affecting all four extremities was collected by questionnaire. Subjects were asked about the extent of disability in each extremity (no disability, some, moderate, cannot or very difficult to use extremity) and the reason for the disability. The functional level was defined using a disability score, calculated by summing the disabilities for upper or lower extremities (no disability, 0; some, 1; moderate, 2; cannot or very difficult to use, 3). Women who scored 0 were classified as 'good', women who scored 1-2 'fair', and who scored 3-6 as 'poor'. RESULTS: Prevalence of disability affecting the upper extremities increased significantly with age (11.9% with some or greater, and 4.3% with moderate or worse). Disabilities of the lower extremities also increased significantly with age (27.2% with some or greater, and 12.9% with moderate or worse), affecting a larger proportion of individuals. With regard to the upper extremities, the women classified a 'fair' and 'poor' increased significantly with age (9.5% with 'fair', and 2.4% with 'poor'), and function decreased (p = 0.003). The same was the case for the lower extremities (19.0% with 'fair', and 8.3% with 'poor') (P < 0.001). The most frequently cited cause of disability was arthritis, both in the upper (20%) and lower (40%) extremities, followed by stroke (10%), fracture (10%) and trauma not associated with fracture (10%). CONCLUSIONS: In middle aged and elderly women, disabilities of the upper and lower extremities become more prevalent and are associated with further functional impairment with aging. Such disabilities are more common in the lower extremities, and arthritis seems to be the most frequent cause.

Stiffness index of the calcaneus measured by quantitative ultrasound and menopause among Japanese women: The Hizen-Oshima Study.

Quantitative ultrasound (QUS) is a recently developed technique for evaluating fracture risk that can assess both bone mass and architecture. Although numerous studies have shown that menopause is associated with accelerated loss of bone mineral density, there are only a few studies on the association of QUS parameter (stiffness index) with menopausal status, especially among Japanese population. We examined age-specific changes in stiffness index, and relation with age, body mass index (BMI) and menopausal status among 506 community-dwelling Japanese women aged 40-89 years. Mean age at menopause (standard deviation) among 459 women with natural menopause was 49.4 (4.0) years. Stiffness index significantly decreased with increasing age. Stiffness index among 80-89 years age group was 40% lower, compared with that of 40-49 years age group. The greatest decline among adjacent ten-year age groups in stiffness index (15%) was found between 40-49 and 50-59 years of age. Multiple regression analysis showed that menopause related with decreased stiffness index, independent of age and BMI. Our findings indicate that menopause influences loss of bone mass and induces deterioration of bone trabecular microstructure.

Spontaneous luxation of encapsulated intraocular lens onto the retina after a triple procedure of vitrectomy, phacoemulsification, and intraocular lens implantation.

PURPOSE: To report the clinical and histological findings of a luxated intraocular lens (IOL) in the capsular bag. METHODS: Review of a case. RESULTS: Twenty-three months after a triple procedure of vitrectomy, phacoemulsification, and IOL implantation for diabetic vitreous hemorrhage and cataract, the encapsulated IOL spontaneously luxated. Scanning electron microscopy showed sparsely distributed anterior and equatorial zonules, with only a few posterior zonules on the surface of the removed capusular bag. CONCLUSION: The absence of the anterior hyaloid membrane and posterior zonules and contraction of the lens capsule may cause dialysis of the zonules. Therefore, the anterior hyaloid membrane should be left in place in patients at low risk for the development of postoperative proliferation to maintain the long-term stability of the IOL.

Knowledge and attitudes toward AIDS among female college students in Nagasaki, Japan.

This study assesses knowledge and attitudes concerning HIV infection and individuals with AIDS among 383 female students attending colleges in Nagasaki, Japan. A structured questionnaire containing questions concerning knowledge about AIDS, sources of information, beliefs and attitudes toward people with HIV/AIDS was administered during sessions set up for that purpose. The mean age of participants was 18.8 +/- 0.8 years (+/- SD). The main source of information for AIDS awareness as reported by the students was the mass media. Good knowledge about AIDS was positively associated with ease of acceptance of living in the same house with a person diagnosed with AIDS [odds ratio (OR): 1.90; 95% confidence interval (CI): 1.07-3.38]. However, residing at home (OR: 0.64; 95% CI: 0.42-0.98) and involvement in nurse education programmes (OR: 0.59; 95% CI: 0.37-0.95) showed a negative association. Students demonstrated a high level of knowledge concerning AIDS and HIV, but had considerable misconceptions and prejudices about people having HIV/AIDS. Our results suggest that a more appropriate education programme in colleges in Japan may be necessary to reduce the discrepancy between general knowledge and desirable attitude regarding HIV/AIDS.

Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alpha5beta1: structural characteristics of heparan sulfate chains with avidity to COOH-terminal heparin-binding domain of fibronectin.

The present study provides direct evidence that syndecan 2 participates selectively in the induction of stress fiber formation in cooperation with integrin alpha5beta1 through specific binding of its heparan sulfate side chains to the fibronectin substrate. Our previous study with Lewis lung carcinoma-derived P29 cells demonstrated that the cell surface heparan sulfate proteoglycan, which binds to fibronectin, is syndecan 2 (N. Itano et al., 1996, Biochem. J. 315, 925-930). We here report that in vitro treatment of the cells by antisense oligonucleotide for syndecan 2 resulted in a failure to form stress fibers on fibronectin substrate in association with specific suppression of its cell surface expression. Instead, localization of actin filaments in the cytoplasmic cortex occurred. A similar response of the cells was observed when the cells were treated to eliminate functions of cell surface heparan sulfates, including exogenous addition of heparin and pretreatment with anti-heparan sulfate antibody, F58-10E4, and with proteinase-free heparitinase I. Size- and structure-defined oligosaccharides prepared from heparin and chemically modified heparins were utilized as competitive inhibitors to examine the structural characteristics of the cell surface heparan sulfates involved in organization of the actin cytoskeleton. Their affinity chromatography on a column linked with a recombinant H-271 peptide containing a C-terminal heparin-binding domain of fibronectin demonstrated that 2-O-sulfated iduronates were essential for the binding. Inhibition studies revealed that a heparin-derived dodecasaccharide sample enriched with an IdoA(2OS)-GlcNS(6OS) disaccharide completely blocked binding of the syndecan 2 ectodomain to immobilized H-271 peptide. Finally, the dodecasaccharide sample was shown to inhibit stress fiber formation, triggered by adhesion of P29 cells to a CH-271 polypeptide consisting of both the RGD cell-binding and the C-terminal heparin-binding domains of fibronectin in a fused form. All these results consistently suggest that syndecan 2 proteoglycan interacts with the C-terminal heparin-binding domain of fibronectin at the highly sulfated cluster(s), such as [IdoA(2OS)-GlcNS(6OS)](6) present in its heparan sulfate chains, to result in the induction of stress fiber formation in cooperation with integrin alpha5beta1.

Demographic and reproductive factors for high seroprevalence of Chlamydia trachomatis among pregnant women in Japan.

In order to elucidate demographic and reproductive factors associated with Chlamydia trachomatis seropositivity, serological screening and questionnaire survey were conducted on pregnant women in Nagasaki Prefecture, Japan. Serum samples were taken from 1718 pregnant women between September and December, 1996, at the cooperative obstetric hospitals and clinics, and tested for the presence of antibodies to C. trachomatis using the enzyme immunoassay. A questionnaire was administered on a sub-sample (n -409), among whom 85 (20.8%) were seropositive. A multiple logistic analysis revealed that four characteristics showed a significant association with the seropositivity: (i) experience of premarital pregnancy, (ii) non use of condoms, (iii) short duration of education, and (iv) more frequent induced abortion. The unsafe sexual behavior of young people lacking proper knowledge of how to prevent STD is the most important intervention target for control of the C. trachomatis epidemic in Japan.

Abnormal fatty acid metabolism in patients with coronary vasospasm.

Although various noninvasive methods have been used to detect vasospasm, none of them are sensitive enough for patients with sporadic attacks. Since abnormal fatty acid metabolism is observed in ischemic myocardium, 123I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a radiolabeled fatty acid analog, has recently been proposed as a useful tracer for detecting myocardial damage. The aim of this study was to clarify the clinical implications of decreased myocardial BMIPP uptake in patients with vasospastic angina. We evaluated 53 patients with vasospastic angina (32 with clinically documented vasospasm [Group-A] and 21 with vasospasm induced by ergonovine provocation [Group-B]) and 27 control subjects, 20 in Group-A were re-evaluated 6 months after medical treatment. The territorial regions of vasospasm-induced coronary artery, the wall motion by left ventriculography, and BMIPP uptake were compared. Vasospasm was induced in multiple coronary arteries in 29 (55%) patients. Reduced wall motion and decreased BMIPP uptake were observed in 19 (36%) patients and 47 (89%) patients, respectively. The sensitivity and specificity of determination of vasospasm-induced coronary arteries with BMIPP scintigraphy were 71% (69/97 coronary arteries) and 88% (126/143), respectively. Vasospasm was re-induced by ergonovine provocation in 8 patients (Group-I) and not re-induced in 12 (Group-II) after treatment. In Group-I, improvement of decreased BMIPP uptake was lower than in Group-II (19+/-11 vs. 59+/-22%, mean+/-SD, p < 0.001). The regions in which vasospasm was re-provoked exhibited decreased BMIPP uptake. Abnormal fatty acid metabolism was more often observed than wall motion abnormality in the vasospastic region in patients with vasospastic angina. BMIPP scintigraphy is a highly accurate and non-invasive technique for determining the presence and location of vasospasm.