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Lymph nodes (LN) and lymphatic drainage were identified by lymphoscintigraphy using ⁹⁹(m)Tc-phytate in order to map the sentinel lymph nodes (SLNs) in patients with malignant skin neoplasms of the lower extremities, and to compare the results with an atlas of Japanese lymphatic anatomy.Sentinel lymphoscintigraphs of 18 patients with malignant skin neoplasms of the lower extremities (9 men, 9 women; age range 45-84 years, mean age 66 years) were analyzed retrospectively, and the LNs detected were identified as SLNs or secondary nodes.The patterns of lymphatic drainage were divided into three different categories: (1) initial drainage into inguinal LN without visualization of popliteal LNs (inguinal type), (2) initial drainage into popliteal LNs and then into intrapelvic LNs (popliteal type), and (3) initial drainage into both popliteal and inguinal LNs (inguinal and popliteal type). More than half of the cases were the inguinal and popliteal type, as both inguinal and popliteal LNs were identified as SLNs. In the cases in which the hallux and its surrounding area were injected, all were the inguinal type and popliteal LNs were not visualized. In one case, only dynamic images detected lymphatic drainage without visualization of popliteal LNs. In contrast to the previously published literature on Japanese lymphatic anatomy, SLN lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, in agreement with currently accepted anatomy, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area. The present results suggest that it is important to confirm lymphatic drainage in order to identify SLNs in the lower extremities.The patterns of lymphatic drainage from the skin of the foot were divided into three different categories. In contrast to previously published Japanese lymphatic anatomy, lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area in agreement with currently accepted Japanese lymphatic anatomy. It is important to confirm lymphatic drainage to identify SLNs in the lower extremities.

Heavy ion beams are a high-LET radiation that has greater biological effect than electron beams or X-rays. However, little is known about the effect of heavy ion beams on the proliferation and differentiation of human hematopoietic stem/progenitor cells (HSPCs). The present study examined the effect of heavy ion beams on gene expression in human HSPCs, especially during early stage of megakaryocytopoiesis. Human CD34+ cells were exposed to monoenergetic carbon-ion beams (290 MeV/nucleon, LET = 50 KeV/m) that were generated by an accelerator (Heavy Ion Medical Accelerator in Chiba). The expression of various genes related to early hematopoiesis, megakaryocytopoiesis/erythropoiesis, cytokine receptors and oxidative stress were analyzed by real-time RT-PCR. Friend leukemia virus integration 1, an early hematopoiesis-related gene, showed significantly higher mRNA expression than the control at 6 hr after irradiation. In contrast, no significant differences were observed in almost all of the other early hematopoiesis-related genes, cytokine receptor-coded genes and megakaryocytopoiesis/erythropoiesis-differentiation pathway-related genes, respectively. An analysis of the response of the genes to oxidative stress revealed the expression of heme oxygenase 1 to show a 1.5-fold and 11.9-fold increase from the day 0 control at 24 hr after 0.5 Gy and 2 Gy irradiation, respectively. Similarly, the NAD(P)H dehydrogenase-quinone 1 expression also showed a 22.0-fold and a 21.8-fold increase at 6 hr in comparison to the initial control. These results showed that the heavy ion beams affect megakaryocytopoiesis/ erythropoiesis differentiation of human HSPCs on the gene expression level.

Hematopoietic stem/Progenitor cells/Cytokine combination/Megakaryocytopoiesis and thrombopoiesis. To evaluate whether the continuous treatment of two cy tokine combinations is effective in megakaryocytopoiesis and thrombopoiesis in hematopoietic stem/progenitor cells exposed to heavy ion beams, the effects of a 2-step culture by a combination of recombinant human interleukin-3 (IL-3) + stem cell factor (SCF) + thrombopoietin (TPO), which just slightly protected against carbon-ion beam-induced damages, and a combination of IL-3 + TPO, which selectively stimulated the differentiation of the hematopoietic stem/progenitor cells to megakaryocytes and platelets, were examined. CD34 + -hematopoietic stem/progenitor cells isolated from the human placental and umbilical cord blood were exposed to carbon-ion beams (LET = 50 keV/μm) at 2 Gy. These cells were cultured under three cytokine conditions. The number of megakaryocytes, platelets and hematopoietic progenitors were assessed using a flow cytometer and a clonogenic assay at 14 and 21 days after irradiation, respectively. However, the efficacy of each 2-step culture was equal or lower than that of using the IL-3 + SCF + TPO combination alone and the 2-step culture could not induce megakaryocytes and platelets from hematopoietic stem/progenitor cells exposed to high LET-radiation such as carbon-ion beams. Therefore, additional cytokines and/or hematopoietic promoting compounds might be required to overcome damage t o hematopoietic cells by high LET radiation.

application/pdf, To clarify whether SEA can aff ect any changes of cellular signalling pathways in intestinal epithelial cells, weperformed experiments to see if SEA can modulate the intracellular signaling pathway in intestinal epithelial cells. Wedemonstrate here that SEA induces an increase in intracellular calcium（ ［Ca2+］i） in human intestinal epithelial cells andthe［ Ca2+］i is released from intracellular stores. SEA-induced increase of［ Ca2+］i was clearly inhibited by treatment witha nitric oxide synthase（ NOS） inhibitor, NG-monomethyl-L-arginine. Intestinal epithelial cells express endothelial NOS（eNOS） in resting cell condition, and express inducible NOS（ iNOS） after stimulating with tumor necrosis factor（ TNF）-α. TNF-α-pretreated cells showed a signifi cant increase in［ Ca2+］i that was also inhibited by the NOS inhibitor. Theseresults demonstrate that SEA induces an increase in intracellular Ca2+ concentration in human intestinal epithelial cells,and the expressions of both eNOS and iNOS could be responsible for the increase in intracellular Ca2+ concentration inthe cells induced by SEA. It is important to study the relationship of NOS expression, Ca2+ signal pathway and emesisfor understanding the mechanism of SEA-induced food poisoning., 弘前医学. 59(Suppl.), 2007, p.S219-S226

The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system. The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54 Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment. The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series. The stereotactic body radiotherapy of 54 Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors.

We evaluated the arteriovenous contrast on the source images of intracranial three-dimensional computed tomography (CT) angiography (3D-CTA) using a high-concentration (370 mg I/ml) contrast agent in comparison with intermediate-concentration (300 mg I/ml) contrast.With a fixed intravenous injection rate and scanning delay, 3D-CTA was performed using a single-detector helical CT scanner in 30 consecutive patients. We used 100 ml of iohexol 300 for 10 patients, 100 ml of iopamidol 300 for 10 patients, and 80 ml of iopamidol 370 for 10 patients. Attenuation values of the bilateral internal carotid arteries, bilateral middle cerebral arteries, basilar artery trunk, bilateral cavernous sinuses, bilateral basal veins, and Galenic vein were measured quantitatively on the axial CT angiographic source images.High-concentration contrast significantly increased the attenuation values of the intracranial arterial system without increasing the attenuation of the venous system.High-concentration contrast is helpful for obtaining valuable arteriovenous contrast on source images with intracranial 3D-CTA.

NF- κ B/Split-dose irradiation/LS174T cells. Although radiation-induced gene expression has been extensively studied, most of the studies to date have focused on that after single-dose irradiation. As split-dose irradiation, rather than single-dose irradiation, is usual in clinical situations, we investigated the effects of split-dose irradiation on nuclear factor κ B (NF- κ B) in the human rectum carcinoma cell line, LS174T. After either single- or split-dose irradiation with a different interval, nuclear localization of NF- κ B was examined by Western blot and immunofluorescence and its DNA-binding activity was measured by ELISA-based assay. Irradiation-induced NFκ B nuclear accumulation and DNA binding activity increased in a dose-dependent manner. The peak of NF- κ B nuclear accumulation and DNA binding activity was seen 2 to 6 hours after a single dose of 4 Gy irradiation and returned to control levels after 12 hours. In split-dose irradiation, NF- κ B activity was similar after the first and second doses of 4 Gy irradiation separated by 12 hours. In addition, NF- κ B activity was decreased by lengthening the interval between irradiation. The cell survival, which was assessed by colony formation assay, showed inverse correlation to this: the surviving fraction was higher after splitdose irradiation than after single-dose irradiation of the same total dose and it increased as the interval between irradiation was lengthened. Thus the present results showed a correlation between NF- κ B activation and the repair of sublethal damage in split-dose irradiation.

We have redeveloped a high-energy x-ray spectra estimation method reported by Iwasaki et al. [A. Iwasaki, H. Matsutani, M. Kubota, A. Fujimori, K. Suzaki, and Y. Abe, Radiat. Phys. Chem. 67, 81-91 (2003)]. The method is based on the iterative perturbation principle to minimize differences between measured and calculated transmission curves, originally proposed by Waggener et al. [R. G. Waggener, M. M. Blough, J. A. Terry, D. Chen, N. E. Lee, S. Zhang, and W. D. McDavid, Med. Phys. 26, 1269-1278 (1999)]. The method can estimate spectra applicable for media at least from water to lead using only about ten energy bins. Estimating spectra of 4-15 MV x-ray beams from a linear accelerator, we describe characteristic features of the method with regard to parameters including the prespectrum, number of transmission measurements, number of energy bins, energy bin widths, and artifactual bipeaked spectrum production.

In the present study, we investigated whether X-irradiated hematopoietic stem cells can be induced to undergo megakaryocytopoiesis and thrombopoiesis in vitro using cytokine combinations that have been demonstrated to be effective for conferring increased survival on irradiated human CD34(+) megakaryocytic progenitor cells (colony-forming unit megakaryocytes; CFU-Meg), such as thrombopoietin (TPO), interleukin 3 (IL3), stem cell factor and FLT3 ligand. Culture of nonirradiated CD34(+) cells in serum-free medium supplemented with multiple cytokine combinations led to an approximately 200- to 600-fold increase in the total cell numbers by day 14 of culture. In contrast, the growth of X-irradiated cells was observed to be one-sixth to one-tenth that of the nonirradiated cultures. Similarly, total megakaryocytes were increased by 50- to 130-fold, while culture of X-irradiated cells yielded one-fourth to one-eighth of the control numbers. At this time, CD41(+) particles, which appeared to be platelets, were produced in the medium harvested from nonirradiated and irradiated cultures. Although radiation suppressed cell growth and megakaryocytopoiesis, there were no significant differences in thrombopoiesis between the two types of culture. These results suggest that X-irradiated CD34(+) cells can be induced to undergo nearly normal terminal maturation through megakaryocytopoiesis and thrombopoiesis by stimulation with appropriate cytokine combinations.

Purpose: To evaluate the efficacy and toxicity of hypofractionated conventional conformation radiotherapy (HCCRT) with noninvasive fixation of the skull on patients with single or several brain metastases. Methods and Materials: The subjects were 44 patients who had three or fewer brain metastases (26 solitary, 18 multiple). Treatment was conducted on 65 metastases by rotational conformal beam or multiple fixed coplanar beams with a standard linear accelerator. The planning target volume consisted of the tumor and a 1-cm safety margin. The median isocentric dose was 24 Gy (range, 18–30 Gy) in 3–5 fractions. Whole-brain irradiation was not applied as an initial treatment. Results: Actuarial local tumor control rates at 6 months and 1 year were 78.4% and 71.9%, respectively. In-field recurrence was noted in 10 of 65 tumors, and repeat HCCRT was applied in 5 tumors. Actuarial overall survival rates at 1 year, 2 years, and the median survival time were 50.8%, 24.1%, and 5.8 months, respectively. The patients with an active primary cancer and poor performance status had a poorer prognosis than those without those factors. Actuarial freedom from second brain metastases rates at 6 months, 1 year, and 2 years were 86.6%, 69.0%, and 40.9%, respectively. Second brain metastases were observed in 9 of 44 patients. Lung adenocarcinomas had a higher risk of second brain metastasis than others. Treatment-related severe early or late complications were not observed in this series. Conclusions: Hypofractionated conventional conformation radiotherapy achieved sufficient tumor control and survival. The results suggest that HCCRT would be one of the alternatives for patients with either solitary or several brain metastases.

On the basis of X-ray spectra information for 4, 10 and 15 MV X-rays from a linear accelerator, we propose a method for formulating the attenuation coefficient in water as a function of depth and off-axis distance. It was confirmed by transmission measurement that the formulation provides a good estimation of the attenuation coefficient in water. Using the formulation, we further assessed the effective attenuation coefficient in water as a function of off-axis distance.

Leptin is an adipocyte-derived hormone that regulates a number of physiological functions, including energy homeostasis and immune function. In immune responses, leptin plays a role in the induction of inflammation. We investigated a role of leptin in Listeria monocytogenes infection using leptin receptor–deficient db/db mice and leptin-deficient ob/ob mice. These mutant mice were highly susceptible to L. monocytogenes, and the elimination of bacteria from the liver was inhibited. After infection, the induction of monocyte chemoattractant protein-1 (MCP-1) and KC mRNA in the liver of db/db mice and the MCP-1 mRNA expression in the liver of ob/ob mice was decreased compared with their heterozygote littermates. Leptin replacement in ob/ob mice resulted in improvement of anti-listerial resistance and the MCP-1 mRNA expression. The elimination of L. monocytogenes was significantly enhanced, and the expression of MCP-1 and KC mRNA was completely reversed in db/db mice by insulin treatment. These results suggest that leptin is required for host resistance to L. monocytogenes infection and that hyperglycemia caused by leptin deficiency is involved in the inefficient elimination of bacteria from the liver. Moreover, defect of MCP-1 expression in the liver may be involved in the attenuated host resistance in these mutant mice.

The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC).Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated.Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1.Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.

We have remodeled the X-ray spectra estimation method, originally proposed by Waggener et al. (Med. Phys. 26(1999)1269), based on the iterative perturbation technique to minimize differences between measured and calculated transmission curves using low Z attenuators. With our approach, the iterative perturbation cycle is repeated until a reasonable spectrum is obtained. Furthermore, the degree of differences between the measured and calculated transmission curves is also checked using high Z attenuators. The present experimental study, conducted using 4, 10 and 15 MV X-ray beams from a linear accelerator, demonstrated that the spectrum varies strongly with the off-axis distance.

A monoclonal anti-human hemoglobin antibody that cross-reacts with mouse hemoglobin was labeled with Iodine-125 through the Chloramine-T method. The labeled antibody was used in an attempt to recognize bleeding sites from the large bowel in a mouse model, through a non-invasive enema-like study. In vitro experiments after double column chromatography of the labeled antibody and 10% trichloroacetic acid conjugation revealed that about 80% of the radioactivity was incorporated into protein. Inhibition assay containing cold (non-radiolabeled) antibody showed that Iodine-125 radiolabeled antibody preserved its immunoreactivity. Autoradiographs exquisitely demonstrated accumulation of isotope in the corresponding intestinal bleeding areas. These findings suggest that this method can be useful for scintigraphic localization of bleeding sites in the large bowel.

Background. This study was designed to evaluate the feasibility and efficiency of giving cisplatin, etoposide, and OK432 concurrently with conventional radiotherapy (RTx) for patient's with inoperable stage III, based on the TNM classification according to the International Union against Cancer staging system for lung cancer (1987) non-small cell lung cancer (NSCLC).

We investigated whether expressions of MHC class I and class II antigens relevant to tumor antigen presentation were changed on human tumor cells cultured with or without recombinant human IL-12(rhIL-12). We showed that the expression of MHC class I antigen on UTC-8, 28-1Cl and SBC-3 cells was augmented when these cancer cells were cultured with rhIL-12. The expression of class II antigen was slightly raised on UTC-8 and 28-1Cl cells by rhIL-12, but not enhanced on SBC-3 cells. These results suggest that rhIL-12 may provide possible enhancement of immunologic tumor recognition, and cytotoxic activity of lymphocytes against tumors through the enhanced expression of MHC class I antigen.

An efficient synthesis of [fluoroacetyl-18F]fluoromelatonin (Nω-[18F]Fluoroacetyl-5-methoxytryptamine) starting from [18F]fluoride and ethyl p-toluensulfonyloxyacetate is described. The total time required for its synthesis is ca. 90 min. The radiochemical yield, purity and specific activity (end of bombardment) of the desired compound are 14.2%,>98%, and 540 mCi/μmol, respectively.

The effect of twice-a-day irradiation on the foot reaction was studied in C3Hf/Sed mice. A numerical scoring system was used to evaluate the foot reaction that became visible shortly after irradiation. Peak reaction occurred on the 21st to 23rd day and reappeared after approximately the 200th postirradiation day. These reactions are called early- and late-appearing reactions, respectively. Animals studied for early-appearing reactions were continuously scored for more than 600 days after irradiation. The late-appearing reaction increased continuously or remained constant, but never decreased during the course of the experiments. Animal feet were irradiated with a fraction size from 1.0 to 5.0 Gy twice-a-day daily with a treatment interval of 6 and 18 hours, and varying numbers of fractions were given. A top-up dose of 20 Gy was given as the last dose. The late-appearing foot reaction following a fraction size of 1.5 Gy or greater increased with increasing total dose. However, the increase in the late reaction score with increasing total dose was trivial following multiple doses with a fraction size of 1.0 Gy, suggesting a possible repopulation during prolonged irradiation or that the observed reaction was a consequential late effect. The Fe-plot based on doses which induced fibrosis in one-half of the irradiated animals, showed an alpha/beta ratio of 6.57 +/- 0.62 Gy, and the presence of a breaking point at approximately 1.5 Gy. The alpha/beta ratios calculated by Joiner's method and Thames direct analysis were identical. The slope of the Fe-plot below 1.5 Gy was significantly steeper than that above 1.5 Gy.

ABE, Y., TAKAHASHI, J., FUKUDA, H. and YOSHIDA, K. Cell Kinetic Study of Murine Jejunal Crypts during Multiple Doses per Day. Tohoku J. Exp. Med., 1992, 168 (2), 311-315- We studied cell kinetics of mouse jejunal crypts during multiple fractionation using double labeling methods. Mice were irradiated to the total body once a day or twice a day. Fraction size was 2 Gy. Overall time was 1, 3 and 5 days. Labeling index (LI), duration of S phase (Ts) and potential doubling time (Tpot) were assessed next morning following the irradiation schedule. Mice were administered both bromo-deoxyuridine (BrdUrd) and 3H- Thymidine ([3H]dT) with a constant interval. Removed jejunum were stained with immuno-histochemistry and, then, processed for autoradiography. BrdUrd and [3H]dT LIs were the same and were increased up to 5 days despite the fractionation schedule. After 1 day following 2 fx/day, both Ts and Tpot decreased significantly. For 1 fx/day treatment, neither Tpot nor Ts changed. After 5 day following 1 and 2 fx/day, both Ts and Tpots were the same and Tpots were significantly shorter than that obtained from control. It seems that proliferative responses between 1 and 2 fx/day were different, - cell kinetics; fractionation; labeling index; potential doubling time; jejunal crypt

Tumor hypoxia and angiogenesis associated with malignant progression have been studied widely. The efficacy of angiogenesis inhibition combined with radiotherapy has been demonstrated in cancer treatment. Here, we studied the effect of hypoxia and angiogenesis inhibition on radiation-induced late rectal injury. The rectum of C57BL/6N mice was irradiated locally with a single dose of 25 Gy. Radiation-induced histological changes were examined at 90 days after irradiation by hematoxylin-eosin (H.E.) staining and azan staining. Pimonidazole was administered and its distribution was assayed by immunohistochemistry staining. Expression of transforming growth factor beta1 (TGF-beta1), hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) was assessed on the fibrotic region using real-time PCR and immunohistochemistry. In addition, the effects of TGF-beta, VEGF and HIF-1alpha on radiation-induced injury were investigated by the administration of neutralizing antibody of TGF-beta, antibody of VEGF or YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) which was developed as an agent for inhibiting HIF-1 expression after irradiation respectively. Fibrosis and uptake of pimonidazole were found 90 days after irradiation. The expression of TGF-beta1, HIF-1alpha and VEGF significantly increased with the formation of fibrosis induced by irradiation compared with unirradiated controls. In addition, treatment of neutralizing antibody of TGF-beta, antibody of VEGF or YC-1 reduced the development of radiation-induced injury. Our results suggested that radiation-induced hypoxia may play an important role in late rectal injury. Although the inhibition of HIF-1alpha and VEGF reduced the radiation induced late injury, the precise mechanism is still unclear.

Rapid chemical syntheses of [carbonyl- 11C]melatonin and N-[carbonyl- 11C]acetylserotonin starting from [11C]carbon dioxide are described. The radiochemical yield (based on [carbonyl-11C]-acetic acid), purity, and the specific activity (end of bombardment) of the former are 12%, >98%, and 4.2 Ci/μmol, respectively. The latter is also synthesized with the same radiochemical yield, purity, and specific activity. The total times required for their syntheses are ca. 45 min, respectively.

A rapid chemical synthesis of 2-[carbonyl-11C]acetamido-2-deoxy-D-glucopyranose (N-[carbonyl-11C]acetyl-D-glucosamine) starting from [11C]carbon dioxide is described. The total time required for the synthesis, the radiochemical yield, and purity of the titled sugar are ca. 60 min, 49.5% (based on [carbonyl-11C]acetic acid), and >98%, respectively.

The incidence of a unilateral aplastic distal vertebral artery (VA) has been reported as 0.2% of cases on cerebral angiography. During our daily magnetic resonance (MR) examinations, however, we frequently encounter MR angiograms (MRAs) that do not demonstrate unilateral VA. The purpose of this study was to calculate the frequency of aplastic unilateral distal VA by MR images performed for asymptomatic people.Over a time span of 1 year, 237 asymptomatic people (140 men, 97 women; ages 28-67 years, mean 54.4 years) underwent brain MRI during a "brain check-up examination" in our hospital. To identify an aplastic unilateral distal VA, we retrospectively compared three-dimensional time-of-flight MRA with basiparallel anatomic scanning (BPAS)-MRI which was designed for recognition of the arterial outer contour.Aplasia of the unilateral distal VA was confirmed in 11 persons (4.6%). According to our classification, hypoplastic distal VA in 12 (5.1%) and asymptomatic acquired unilateral distal VA occlusion was also proved in 2 (0.8%).We found that the frequency of aplastic unilateral VA was 4.6% in asymptomatic people using a combination of MRA and BPAS-MRI for assessment of an intracranial VA.

We evaluated the difference in computed tomography (CT) attenuation values of the intracranial arterial and venous systems among the various contrast injection protocols (higher iodine delivery rate or higher concentration of the agent) on the source images of intracranial three-dimensional CT angiography (3D-CTA) using a multidetector-row CT (MDCT) scanner.We used 100 ml of iopamidol 300 at an injection rate of 3.0 ml/s, 100 ml of iopamidol 300 at an injection rate of 3.7 ml/s, and 80 ml of iopamidol 370 at an injection rate of 3.0 ml/s. There were 10 patients in each group. Attenuation values of the bilateral internal carotid arteries (ICAs), basilar artery trunk, bilateral cavernous sinuses (CSs), and Galenic vein were measured quantitatively on the axial CT angiographic source images obtained by four-channel MDCT.Injection of the high-concentration contrast with a higher iodine-delivery rate achieved good arteriovenous contrast at the cavernous portion. With the same rate of iodine delivery, injection of the intermediate concentrate agent increased the CT value of not only the ICAs but also the CSs.High-concentration contrast could increase ICA attenuation without intracavernous attenuation gain during the "first-pass" phase.

Rapid and efficient syntheses of 2-deoxy-2-[18F]fluoroacetamido-D-mannopyranose (1) and -D-galactopyranose (2), respectively, starting from [18F]fluoride and ethyl bromoacetate are described. [18F]Fluoride was produced by the 18O (p, n) 18F nuclear reaction using the cyclotron. The total times required for synthesis of (1) and (2) are ca. 80 min. The radiochemical yield and purity of (1) are an 18% and ≥98%, respectively. Compound (2) is also synthesized with the same radiochemical yield and purity.

We reported the case of an 84-year-old female suffering from chemosis and exophthalmos. Carotid arteriograms revealed a direct carotid-cavernous fistula (CCF) but could not clearly show the fistula point because of its high-flow nature. We then performed three-dimensional computed tomographic angiography (3D-CTA) using a multi detector-row CT (MDCT) scanner. Multi-planar reformatted CT images distinctly revealed a right carotid aneurysm at the cavernous portion and a shunting point between the aneurysm and the cavernous sinus. Based on this information, we opted to performa transvenous coil embolization to treat this patient. Successful selective coil embolization was performed at the fistulous point was done with a smaller number of coils than ordinarily required in sinus packing. Performing 3D-CTA by using a MDCT was helpful in decision making for the selective coil embolization to treat direct CCF.

The aim of this study is to evaluate the individual differences in radiosensitivity of lineage-committed myeloid hematopoietic progenitors, colony-forming cells (CFC), detected in steady-state human peripheral blood (PB). Mononuclear cells were prepared from the buffy-coat of 30 individuals PB, and were assayed for CFC by semi-solid culture supplemented with cytokines. X irradiation was performed in the range of 0.5-4 Gy at a dose rate of about 80 cGy/min. The mean number of hematopoietic progenitor cells is 5866 alpha 3408 in 1 ml of buffy-coat, suggesting that the erythroid progenitor cells are the major population. The total CFC radiosensitivity parameter D(0) and n value are 1.18 alpha 0.24 and 1.89 alpha 0.98, respectively. Using a linear regression analysis, a statistically significant correlation is observed between the D(0) value and the surviving fraction at 4 Gy (r = 0.611 p < 0.001). Furthermore, we evaluate the relationship between individual radiosensitivity and the level of antioxidants, plasma uric acid, plasma bilirubin, and intracellular glutathione. No statistically significant correlations are observed, however, between the D(0) parameter and the level of antioxidants, plasma uric acid, plasma bilirubin, and intracellular glutathione. The present study demonstrates that there are large individual differences in the radiosensitivity of hematopoietic progenitor cells as detected in steady-state human PB. These differences demonstrate almost no correlation with plasma or intracellular antioxidants. The prediction of individual differences in radiosensitivity of CFC can only be measured by 4 Gy irradiation.

Radiation-induced intestinal injury is a common complication in radiotherapy for the cancer located in abdomen or pelvis. However, there is no effective treatment for radiation-induced intestinal injury now. It is therefore important to develop new treatments for radiation-induced intestinal injury. In this study, we investigated whether embryonic stem (ES) cells could be transplanted directly into the radiation-damaged intestine and could colonize and differentiate into the intestinal epithelial cells. The intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy, and were immediately transplanted with male 129/Sv-derived ES cells into the wall of the irradiated intestine by direct injection. The intestine was removed on days 13 to 27 after transplantation. The Y-chromosome DNA of transplanted ES cells in the irradiated intestine was determined by polymerase chain reaction. Colonization and differentiation of transplanted ES cells in the irradiated intestine were analyzed by histological and immunohistochemical methods with antibodies against stage-specific embryonic antigen-1, alpha-smooth muscle actin and cytokeratin AE1/AE3. The cells of donor origin were identified in the intestine of irradiated mice, and intestinal crypt-like structures were observed on day 13 after transplantation. Importantly, we observed that ES cells could differentiate into epithelial cells in the submucosa of irradiated intestine on day 13 and 27 after transplantation. These results suggest that transplanted ES cells could colonize and differentiate in the intestinal intestine. Such a new approach for damaged intestine with transplanted stem cells would be promising.

Heavy ions have a unique efficacy for tumor control in radiotherapy. To clarify the effects of heavy-ion beams on hematopoietic stem/progenitor cells, the effects of carbon-ion beams on megakaryocytopoiesis and thrombopoiesis in CD34(+) cells derived from human placental and umbilical cord blood were investigated. The cells were exposed to carbon-ion beams (LET = 50 keV/microm) and then were treated with thrombopoietin (TPO) alone or TPO plus other cytokines. Megakaryocytic progenitor cells, such as megakaryocyte colony-forming units (CFU-Meg), were far more sensitive to carbon-ion beams than to X rays, and no restoration of carbon-ion beam-irradiated CFU-Meg by treatment with any cytokine combination was observed. However, total cell expansion in liquid culture was not different after either carbon-ion beam or X irradiation of CD34(+) cells. The activation of gamma-H2AX, a marker of DNA double strand-breaks (DSBs), was promoted by the cytokine treatment in X-irradiated CD34(+) cells but not in carbon-ion-irradiated cells. These results showed that carbon-ion beams inflicted severe damage on megakaryocytopoiesis and thrombopoiesis and that a better combination of cytokines and other agents may be needed to stimulate the recovery of hematopoietic cells and repair this damage.

We have redeveloped a high-energy x-ray spectra estimation method reported by Iwasaki et al. [A. Iwasaki, H. Matsutani, M. Kubota, A. Fujimori, K. Suzaki, and Y. Abe, Radiat. Phys. Chem. 67, 81-91 (2003)]. The method is based on the iterative perturbation principle to minimize differences between measured and calculated transmission curves, originally proposed by Waggener et al. [R. G. Waggener, M. M. Blough, J. A. Terry, D. Chen, N. E. Lee, S. Zhang, and W. D. McDavid, Med. Phys. 26, 1269-1278 (1999)]. The method can estimate spectra applicable for media at least from water to lead using only about ten energy bins. Estimating spectra of 4-15 MV x-ray beams from a linear accelerator, we describe characteristic features of the method with regard to parameters including the prespectrum, number of transmission measurements, number of energy bins, energy bin widths, and artifactual bipeaked spectrum production.

Epigallocatechin-3-gallate (EGCg) has been widely recognized as a powerful antioxidant and free radical scavenger. The effects of EGCg on the proliferation and differentiation of X-irradiated megakaryocytic progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) using CD34+ cells prepared from human placental and umbilical cord blood have been shown. In the absence of exogenous thrombopoietin (TPO), no colonies are observed in cultures containing or lacking EGCg (1 nM-100 microM). In the presence of TPO, in contrast, EGCg significantly promotes CFU-Meg-derived colony formations within the 10-100-nM range. A 1.5-fold increase in the total number of CFU-Meg has been counted compared with the control. These favorable effects of EGCg are also observed in the culture of CD34+ cells before and after X irradiation with 2 Gy. Moreover, in order to investigate the function of EGCg promoting megakaryocytopoiesis and thrombopoiesis in ex vivo cultures, both non-irradiated and X-irradiated CD34+ cells are grown in liquid cultures supplemented with TPO. In both cultures, EGCg increases the total number of cells and megakaryocytes. It has been suggested that the favorable effects of EGCg reduce the risk factor from radiation damage in megakaryocytopoiesis.

PURPOSE: Basiparallel anatomic scanning (BPAS)-MR imaging is a simple MR imaging technique that we designed for visualization of the surface appearance of the vertebrobasilar artery within the cistern. It can clearly show the outer contour of occluded arteries or thrombosed aneurysms. By comparing BPAS-MR imaging with 3D time-of-flight (TOF) MR angiography (MRA), we can precisely evaluate the vertebrobasilar artery condition. The purpose of this study is to determine the value of BPAS-MR imaging for brain MR examination. MATERIALS AND METHODS: We obtained BPAS-MR imaging, in addition to 3D TOF MRA, for 385 consecutive patients who underwent brain MR imaging and MRA in our hospital between April 1 and August 31, 2003. Their complaints varied from mild head symptoms to severe neurologic illness. Comparing BPAS-MR imaging with MRA, we revealed the character of BPAS-MR imaging and determined the role and value of displaying vascular outer contour. RESULTS: Although the cases did not represent a restricted group of vertebrobasilar diseases, BPAS-MR imaging contributed to accurate evaluation of the vertebrobasilar artery in 90 of our 385 patients (23.4%). Of particular note, 16.1% of our patients could not be evaluated accurately by MRA only. BPAS-MR imaging was useful to confirm hypoplastic or occluded vertebral arteries and to reveal the whole appearance of large or partially thrombosed aneurysms of the vertebrobasilar system. CONCLUSION: The combination of the BPAS-MR imaging and the 3D TOF MRA was necessary for accurate diagnosis in 16.1% of our ordinary patients. We should evaluate not only MRA but also the vascular outer contour revealed on BPAS-MR imaging, though its application is limited to the vertebrobasilar system and the screening use.

We clarified the images, impressions, and information about radiotherapy in standard Japanese patients and, at the same time, investigated their need for information about radiotherapy, in order to identify what we, as radiation oncologists, should do to decrease patient anxiety and create good physician-patient relationships.We handed out 10 questionnaires to 1529 patients from April 2002 through July 2002 in 22 Japanese institutions that were equipped with radiotherapy machines. Questionnaires contained 10 items asking about patients' background, their impression of radiotherapy, frequency of exposure to information about radiotherapy, need to obtain information about radiotherapy, and ideal additional medical informational resources or their content.About 60% of patients had had the opportunity to obtain information about radiotherapy "sometimes" or "often," but 80% of them were not satisfied with the availability of information and answered that it was inadequate. Ten percent responded that they had no idea about radiotherapy. Thirty percent felt unspecified anxiety concerning radiotherapy, and those who had less chance to be exposed to information about radiotherapy felt more anxiety than the others (33.2% vs. 25.2%, p=0.0008). The need for "explanation and information about adverse effects" was the top priority, followed by "explanation of outcome." Although they generally obtained information from their physician (radiation oncologist), they also wanted additional information via written media (662 patients, 43%). However, patients who were over 60 years old most wanted to obtain additional medical information directly from their own radiation oncologist (37.7%).Information about radiotherapy given to patients and the general public is still insufficient in Japan. To fully utilize radiotherapy, which is a very effective treatment option against cancer, and to reduce anxiety about radiotherapy among cancer patients, more information is necessary.

CD34 antigen is a novel marker for human hematopoietic stem/progenitor cells. In the present study, two cell fractions, CD34low and CD34high, were prepared from steady-state human peripheral blood on the basis of CD34 antigen expression. The colony-forming unit megakaryocytes (CFU-Meg) contained in each cell fraction were compared for X-radiation sensitivity and cytokine action. The content of CD34+CD45+ cells in the CD34low and CD34high cell fractions was 74.8% and 88.8%, respectively, and the frequency of thrombopoietin (TPO)-supported CFU-Meg in the CD34low cell fraction was 1.9 times higher than that in CD34high. The CFU-Meg in CD34high were more radiosensitive than those in CD34low, indicating that steady-state human peripheral blood contains different types of CFU-Meg. However, no significant differences were observed between cell fractions in the radiation survival curves of CFU-Meg stimulated by TPO plus cytokines except granulocyte colony-stimulating factor (G-CSF). TPO plus interleukin 3 was the optimal combination for survival of both types of CFU-Meg after X irradiation. The present study also demonstrated that TPO plus G-CSF is able to increase the survival of irradiated CD34low CFU-Meg. These results suggest that two megakaryocytic progenitor populations with different radiosensitivity and cytokine responses are found in steady-state human peripheral blood.

Radiographic noise properties have been evaluated using the Wiener spectrum. However, this approach is not appropriate for periodic noise for two reasons. One is that it takes infinite values at the spatial frequencies of periodic noise. The other is that when adopting a numerical integration, it allows unstable values at each spatial frequency, depending on the integral region. Introducing three types of spectra (W1, W2, and W3) in connection with the Wiener spectrum, we propose a practical approach to evaluation of periodic noise. Radiographic images sometimes contain noise that is not totally random and not perfectly periodic. Therefore, using the Wiener spectrum and the W1 spectrum, we also propose two factors for evaluation of the degree of random-periodicity of noise containing periodic signals.

To investigate the impact of tumor volume on overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy (RT).Between May 1997 and February 2003, 71 patients with Stage III NSCLC were treated with radiation therapy of 60 Gy or more. The total target dose was between 60 and 77 Gy (average, 66.3 Gy). Chemotherapy was used in 45 cases. The primary tumor and nodal volume were identified in pretreatment computed tomography scans. Univariate and multivariate analyses were used to evaluate the impact of tumor volume on survival after RT.The overall 2-year survival rate was 23%, with a median survival time of 14 months. The median survival times were 10 months and 19 months with large primary tumor volume more than median volume and smaller primary tumor volume, respectively. At a univariate analysis, the total tumor volume (TTV) (p0.0003) and the primary tumor volume (p0.00008) were significant and the nodal volume was not. At multivariate analyses, both the TTV and the primary tumor volume were significant prognostic factors.The primary tumor volume as well as TTV is a significant prognostic factor on survival in patients with Stage III NSCLC treated with RT and should be recorded in clinical results when the survivals are compared among clinical studies.

Graphic noise properties are usually evaluated using the Wiener spectrum. However, this approach is not appropriate for periodic noise for two reasons. One is that it takes infinite values at the spatial frequencies of periodic noise. The other is that when adopting a numerical integration, it allows unstable values at each spatial frequency, depending on the integral region. Introducing three types of spectra (W(1), W(2), and W(3)) in connection with the Wiener spectrum, we propose a practical approach to evaluation of periodic noise. Graphic images sometimes contain noise that is not totally random and not perfectly periodic. Therefore, using the Wiener spectrum and the W(1) spectrum, we also propose two factors for evaluation of the degree of random-periodicity of noise containing periodic signals.

We studied tumor detection by indocyanine green (ICG) with near-infrared topography in rat experimental tumors: hepatoma AH109A and osteosarcoma POB 102. Time-intensity curves and topograms after ICG injection were obtained in tumors and surrounding normal tissues. Intensities in tumors were slowly reduced, and intensities in normal tissues were rapidly reduced, resulting in positive tumor image in topogram. It is concluded that near-infrared topography enhanced by ICG is useful for cancer detection.

The purpose of this study is to confirm whether T2-weighted imaging and perfusion imaging, i.e. autoradiogram of14C-iodoantipyrine, on the course of brain edema correspond to each other or not. Cold injured rat brains were used as a model and were sequentially examined by both methods and compared with each other and with histological specimens. Special focus relies on the time changes in the lesions. High SI of T2-weighted images were observed and the percentages in the high SI area to the total brain area in the same slice were 4.7±0.31, 5.6±0.46 and 3.4±0.42 for 6,24 and 48 hours, respectively. By contrast, low perfusion areas were indicated in the perfusion study and their percentages were 4.6±0.55, 5.6±0.86 and 2.4±0.35 for 6,24 and 48 hours, respectively. At 48 hours after cold injury, low perfusion areas were smaller than high SI areas. Moreover, high accumulation areas consisting of macrophages were observed surrounding necrosis. It is concluded that there is dissociation between perfusion and T2-weighted MR imaging, where the collection of macrophages surrounding edema lesions and necrosis had the same appearance on MRI and different accumulations on perfusion studies.

Using functional magnetic resonance imaging (fMRI), we measured regional blood flow to examine which motor areas of the human cerebral cortex are preferentially involved in an auditory conditional motor behavior. As a conditional motor task, randomly selected 330 or 660 Hz tones were presented to the subjects every 1.0 s. The low and high tones indicated that the subjects should initiate three successive opposition movements by tapping together the right thumb and index finger or the right thumb and little finger, respectively. As a control task, the same subjects were asked to alternate the two opposition movements, in response to randomly selected tones that were presented at the same frequencies. Between the two tasks, MRI images were also scanned in the resting state while the tones were presented in the same way. Comparing the images during each of the two tasks with images during the resting state, it was observed that several frontal motor areas, including the primary motor cortex, dorsal premotor cortex (PMd), supplementary motor area (SMA), and pre-SMA, were activated. However, preferential activation during the conditional motor task was observed only in the PMd and pre-SMA of the subjects' left (contralateral) frontal cortex. The PMd has been thought to play an important role in transforming conditional as well as spatial visual cues into corresponding motor responses, but our results suggest that the PMd along with the pre-SMA are the sites where more general and extensive sensorimotor integration takes place.

A G2 block is a well-known response to irradiation, showing a delay time that depends on the given single dose. Our question was whether the division delay time is the same after multiple doses as after a single dose. We therefore studied mitosis in the mouse jejunal crypt using a quantitative approach. Three radiation schedules with a fraction size of 2 Gy were compared: a single dose and twice-daily irradiation at a 4-h interval for 1 or 3 days. With the single dose, mitotic figures disappeared at 0. 5 h and reappeared after 2h. At the end of each multiple-dose regimen, significant numbers of mitoses could be observed at 0. 5 and 1 h but a trough was seen at 2h, with numbers then increasing again. Calculated average division delays after the single dose and repeated doses for 1 and 3 days were 1. 5, 1.3 and 1.7 h respectively. In summary, most crypt cells treated with multiple fractions remain susceptible to G 2 arrest, showing the same delay time as with the single dose.

Research on selective melanoma neutron capture therapy was initiated by Y. Mishima and his associates, consisting of physicists, chemists, pharmacologists, radiobiologists, and medical scientists. Following basic research of 13 years, this team started the first clinical. trial of melanoma BNCT using10B-paraboronophenylalanine (BPA) in 1987 and have treated 16 patients with various types of melanoma1−4.

The most severe radiation-induced brain damage is brain necrosis. Clinically, it is difficult to differentiate between brain necrosis and recurrent brain tumor1. Radiation brain necrosis is a terminal stage of the brain damage. However, it is not well known the mechanisms underlying the process that produce the brain necrosis after irradiation: i.e. how glucose metabolism and blood flow distribution change after irradiation. We studied the uptake of 18F-2-deoxy-D-glucose (FDG) and 99mTc-hexamethylpropylene amine oxine (HMPAO) in the irradiated brain of the mouse regarding glucose and blood flow distribution, respectively. This study is a feasible for positron emission tomography.

In order to evaluate the role of hexosamine metabolism in tumor tissue, we studied the biodistribution of N-(F-18)-fluoroacetyl-D-glucosamine (FAGlu) in male Donryu rats bearing poorly differentiated hepatomas (AH109A and AH272). Compare with the former result of the high tumor uptake of FAGlu in C3H/He mice bearing well differentiated spontaneous hepatoma, the tumor uptakes of FAGlu in these tumors showed the lower values. This suggested that spontaneous hepatoma maintained a high activity of glucosamine metabolism, while poorly differentiated hepatoma had little activity. Metabolism of glucosamine in tumor tissue may be another marker for characterizing tumors. We also discuss the tissue distribution of new F-18 labeled hexosamines, N-(F-18)-fluoroacetyl-D-mannosamine and N-(F-18)-fluoroacetyl-D-galactosamine in tumor bearing rats.

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10(-3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0.