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.

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.

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.

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.

Frequency of presumed reentry with an excitable gap in sustained ventricular tachycardia unassociated with coronary artery disease.

In sustained ventricular tachycardia (VT) unrelated to coronary artery disease, the incidence of reentry with an excitable gap was examined, and rapid pacing was performed to entrain VT in 48 episodes in 42 consecutive patients. Coronary artery disease was excluded by coronary arteriography. The underlying heart diseases were postoperative congenital heart diseases (n = 5), dilated (n = 7) or hypertrophic (n = 4) cardiomyopathy, arrhythmogenic right ventricular dysplasia (n = 6) and miscellaneous heart diseases (n = 5), as well as no demonstrable heart disease (n = 15) in which 8 patients had verapamil-responsive VT. Except for 1 patient with hypertrophic cardiomyopathy, 48 morphologically distinct monomorphic sustained VTs were induced. Twenty-five VTs showed right bundle branch block morphology and 23 left bundle branch block morphology, and VT was entrained in 84 and 96%, respectively. The overall incidence of the entrainment was 89.6% (43 of 48 monomorphic VTs), and the frequency of the ability to entrain VT ranged between 33.3 and 100% in the subgroups. The lowest frequency was found in hypertrophic cardiomyopathy. In conclusion, most inducible monomorphic sustained VT unassociated with coronary artery disease was presumed to be reentry with an excitable gap.

Ataxic polyneuropathy and anti-Pr2 IgM kappa M proteinemia.

A case of ataxic neuropathy associated with IgM kappa M proteinemia is reported. Double filtration plasmapheresis effectively treated the neuropathy. The IgM kappa antibody had anti-Pr2 cold agglutinin activity. We demonstrated reactivities of the IgM kappa antibody to sialosyl paragloboside, sialosyl lactosaminyl paragloboside, GT1b, GD1a, GD1b, GM3 and GD3 on high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay, which is previously unreported antigenic specificity of the M proteins in cases of paraproteinemic neuropathy. IgM M protein with anti-Pr2 cold agglutinin activity may play a pathogenetic role in peripheral nerve demyelination, because the target antigens of the M protein are present in myelin and possibly in endothelial cells of the peripheral nervous system.

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.

Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue.

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr = 46,000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin (pI = 4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.

Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency.

Long-chain fatty acids (LCFA) are one of the major cardiac energy substrates, so understanding LCFA metabolism may help in elucidating the mechanisms of various heart diseases. CD36 is a multifunctional membrane glycoprotein that acts not only as a receptor for thrombospondin, collagen and oxidized low density lipoprotein but also as a receptor for LCFA. We investigated the relationship between CD36 expression in myocardial capillary endothelial cells and myocardial LCFA uptake in patients with CD36 deficiency. We analyzed CD36 expression in blood cells from 250 patients with heart diseases by means of a flow cytometer. In 218 patients, myocardial LCFA scintigraphy was performed with 123I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP). In 5 patients, myocardial capillary endothelial cells were examined immunohistochemically for CD36 expression. Eleven patients (4%) showed signs of type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Twenty patients (8%) had type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 11 patients with type I CD36 deficiency, no BMIPP accumulation was observed in the heart, but in 13 patients with type II CD36 deficiency, BMIPP accumulation in the heart was focally reduced, but there were no patients without BMIPP accumulation in the heart. Although the myocardial capillary endothelial cells from two CD36-positive patients expressed CD36, those from two patients with type I CD36 deficiency did not. In a patient with type II CD36 deficiency, some capillary endothelial cells displayed patchy CD36 expression. CD36 deficiency was documented in 31 (12%) patients with heart diseases. Because CD36 was not expressed in the myocardial capillary endothelial cells in patients with type I CD36 deficiency, type I CD36 deficiency is closely related to lack of myocardial LCFA accumulation and metabolism in the myocardium.

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.

[A case of Marshall syndrome with secondary glaucoma due to spontaneous rupture of the lens capsule].

An eight-year-old boy developed acute glaucoma in his left eye. He was diagnosed as having Marshall syndrome because of bilateral cataract, high myopia, saddle nose, hypertelorism, and lack of arthropathy. When seen immediately after the glaucomatous attack, the affected eye showed ruptured anterior and posterior lens capsules and displacement of the lens nucleus into the anterior chamber and vitreous cavity. Lens extraction and vitrectomy induced normalization of intraocular pressure and visual acuity. There are forty cases reported in the world literature and only one cases in Japan. To the best of our knowledge, this is the first case treated successfully by vitreous surgery.

[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.

[Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency].

A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.

[Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency].

The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases [44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases] using a flow cytometer. 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases.

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.