Yoshinao Abe

Effects of smoking on regional cerebral blood flow in neurologically normal subjects.

The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects, were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. One hundred and eleven subjects, who had no abnormalities in neurological examinations nor in CT scans, were divided into two groups: smokers (37) and non-smokers (74). Those who had a smoking index (Number of cigarettes/day) × (years of smoking history) greater than 200 were designated as smokers. The mean smoking index of smokers was 760. Sixty-two of the 74 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 17. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF, 12.5% lower in smokers, p less than 0.001). Increased reduction of CBF with advancing age was also observed. Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduces CBF. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels.

Differential diagnosis of solitary pulmonary nodules with positron emission tomography using [11C]L-methionine.

Two patients with solitary pulmonary nodules, 1.5-2.0 cm in diameter, were studied by positron emission tomography using [11C-Methyl]L-methionine (11C-Met). Case 1 showed high accumulation of 11C-Met in the tumor, and a tumor/muscle ratio of 6.0 suggesting malignancy. Tissue obtained by biopsy revealed a squamous cell carcinoma. Case 2 showed nonspecific isotope accumulation in the tumor, and a tumor/muscle ratio of 1.2 suggesting a benign lesion. Lung biopsy demonstrated granuloma. Positron emission tomography with 11C-Met seems to be useful for the differential diagnosis of solitary lung nodules.

Clinical outcome of stereotactic body radiotherapy of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system

PurposeThe 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.Methods and materialsThe 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.ResultsThe 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.ConclusionThe 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.

Regeneration of megakaryocytopoiesis and thrombopoiesis in vitro from X-irradiated human hematopoietic stem cells

Abstract Kashiwakura, I., Inanami, O., Abe Y., Satoh, K., Takahashi, T. A. and Kuwabara, M. Regeneration of Megakaryocytopoiesis and Thrombopoiesis In Vitro from X-Irradiated Human Hematopoietic Stem Cells. Radiat. Res. 166, 345–351 (2006). 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.

Staphylococcal enterotoxin A modulates intracellular Ca2+ signal pathway in human intestinal epithelial cells.

We demonstrate here that staphylococcal enterotoxin A (SEA) induces an increase in intracellular calcium ([Ca2+]i) in human intestinal epithelial cells and the [Ca2+]i is released from intracellular stores. SEA‐induced increase of [Ca2+]i was clearly inhibited by treatment with a nitric oxide synthase (NOS) inhibitors, N G‐monomethyl‐L‐arginine and guanidine. Intestinal epithelial cells express endothelial NOS in resting cell condition, and express inducible NOS after stimulating with tumor necrosis factor (TNF)‐α. TNF‐α‐pretreated cells showed a significant increase in [Ca2+]i that was also inhibited by the NOS inhibitor. These results suggest that SEA modulated [Ca2+]i signal is dependent on NOS expression in human intestinal epithelial cells.

Correlations between Regional Cerebral Blood Flow and Age-related Brain Atrophy: A Quantitative Study with Computed Tomography and the Xenon-133 Inhalation Method

One hundred and two subjects (40 men and 62 women) neither having a history of neurologic deficits nor showing organic lesions on computed tomographic examination of the brain were studied. Ages of the subjects ranged from 26 to 81 years. Regional cerebral blood flow was measured by the xenon‐133 inhalation method, and the volume percentage of brain with respect to the cranial cavity (craniocerebral index) was calculated by means of computer programs. Regional cerebral blood flow was computed as the fast component of two‐compartmental analysis and as the initial slope index value. The percentage of each subjects craniocerebral index in relation to the standard for subjects with non‐atrophied brains (brain volume index) was calculated as the indicator of brain atrophy. Both the mean brain fast component values and the mean brain initial slope index values correlated closely with the brain volume index in the elderly (r = 0.60, r = 0.62; P < 0.0001 in each correlation coefficient). Low cerebral blood flow values coincided with loss of brain substance in the final stage of age‐related brain atrophy, but not in the intermediate stage.

Incidence of unilateral distal vertebral artery aplasia: evaluation by combining basiparallel anatomic scanning-magnetic resonance imaging (BPAS-MRI) and magnetic resonance angiography

PurposeThe 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.Materials and methodsOver 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.ResultsAplasia 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%).ConclusionWe 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.

Severe Damage of Human Megakaryocytopoiesis and Thrombopoiesis by Heavy-Ion Beam Radiation

Abstract Takahashi, K., Monzen, S., Eguchi-Kasai, K., Abe, Y. and Kashiwakura, I. Severe Damage of Human Megakaryocytopoiesis and Thrombopoiesis by Heavy-Ion Beam Radiation. Radiat. Res. 168, 545–551 (2007). 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/μm) 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 γ-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.

Tumor uptake studies of S-adenosyl-l-[methyl-11C]methionine and l-[methyl-11C]methionine

Tumor accumulation of S-adenosyl-L-[methyl-11C]methionine ([11C]SAM) was investigated in mice bearing mammary carcinoma (FM3A) and in rats bearing ascitic hepatoma (AH109A). After injection of [11C]SAM the blood clearance of 11C radioactivity was rapid. The 11C level was relatively high in both tumors. The uptake ratios of tumor to organ increased with time in several organs, especially in brain and muscle. In FM3A tumor tissue the 11C was incorporated with time into the acid-precipitable fraction and 38% of the 11C was detected in this fraction at 60 min after injection. This fraction reflects the amount of 11C-methyl group transferred into macromolecules in tumor tissue. In AH109A-bearing rats the metabolisms of [11C]SAM and L-[methyl-11C]methionine ([11C]Met), in vivo precursor of SAM, were compared. Tumor uptake of [11C]SAM was about two thirds of that of [11C]Met at 20 min after injection. At this time, for the [11C]SAM 27 and 8% of the 11C in the AH109A tissue were detected in the acid-precipitable and the lipid fractions, respectively. The corresponding figures for [11C]Met were 61% and 2%. In the liver considerable amounts of 11C were observed in the lipid fraction for both tracers. These results show that [11C]SAM has potential as a tracer for tumor localization with positron emission tomography (PET) and suggest that in tumor studies combining [11C]Met and PET, it should be taken into account that the 11C-labeled methyl group of [11C]Met is not only incorporated into protein but also other macromolecules and lipids via [11C]SAM.

Characteristic features of a high-energy x-ray spectra estimation method based on the Waggener iterative perturbation principle.

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.