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H Sakahara

Publications and source records attributed to H Sakahara.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gadolinium-enhanced MR angiography in the evaluation of congenital cardiovascular disease pre- and postoperative states in infants and children.

The purpose of this study was to evaluate the utility of dynamic contrast magnetic resonance (MR) angiography under sedation for assessing congenital cardiovascular disease in infants and small children before and after cardiac surgery. In 38 patients with cardiovascular abnormalities, thoracic vasculatures were evaluated in either the preoperative (group 1; 23 patients, median age 9 months old) or the postoperative (group 2; 15 patients median age 1. 3 years old) state using gadolinium-enhanced dynamic MR angiography. Acquired data were processed with a multiprojection volume reconstruction. Image quality (grades 1-5, undiagnostic to excellent), presence or absence of the extracardiac vasculature, its pathology (group 1), and the patency of the postsurgical shunt or reconstructed vasculature (group 2) were evaluated. All images were of diagnostic image quality (mean grade 4.4-3.2). Recognition of the thoracic vasculature was correctly made in all cases (38/38, 100%). In group 1, anomalies and pathologic changes were correctly identified in 22 of 23 cases (95.7%). In one patient with dextrocardia and the cardiac type of total anomalous pulmonary venous return, the abnormality was not recognized. In group 2, the patency of the shunt flow after Glenn (n = 6), modified Fontan (n = 4), Rastelli (n = 1), and Blalock-Taussig (n = 3) operations was well demonstrated in each case. The reconstructed pulmonary artery (n = 1), veins (n = 2), and aorta (n = 1) were correctly visualized. In one case, stenosis of the reconstructed left pulmonary vein was missed by MR angiography. In 14 of 15 cases in group 2 (93.3%), MR angiography correctly gave information on the operated areas. In conclusion, dynamic contrast MR angiography under sedation is useful for evaluation of the thoracic vasculature of infants and small children in the pre- and postoperative states. J. Magn. Reson. Imaging 2000;12:1034-1042.

Aortography↗
PubMed2000

FDG-PET of autoimmune-related pancreatitis: preliminary results.

The purpose of this retrospective study was to elucidate the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings in autoimmune-related pancreatitis (AIP), which is a reversible chronic pancreatitis with an autoimmune cause. The study group comprised six patients with clinically diagnosed AIP. After 370 MBq (10 mCi) of FDG had been injected intravenously, the abdomen and/or the whole body was scanned at 1 h post injection in all patients, and scanning was repeated at 2 h in four patients. PET findings were evaluated visually and/or semiquantitatively using the standardized uptake value (SUV). In four of the six patients, PET demonstrated intense uptake in the whole pancreas, which appeared swollen on computed tomography, and the accumulation increased with time in three patients. In one patient, intense focal uptake in the pancreatic head was observed, and the accumulation decreased over time. In the remaining patient, no abnormal accumulation in the pancreas was observed. Follow-up PET scanning after steroid therapy was performed in three patients, and intense FDG uptake was no longer observed. Our preliminary data show that AIP can cause intense FDG uptake in the pancreas. This fact, and the benign status of the condition, should be kept in mind when making a diagnosis with FDG-PET in patients with pancreatic disorders.

Cell Survival↗
PubMed2000

Post-stimulus response in hemodynamics observed by functional magnetic resonance imaging--difference between the primary sensorimotor area and the supplementary motor area.

The blood oxygen level dependency (BOLD) contrast is a useful tool for functional neuroimaging based on the hemodynamic response to neuronal activation. We observed different hemodynamic responses in the BOLD signal between the primary sensorimotor area (SM1) and the supplementary motor area (SMA) in the sequential finger movement task. In the SMA, a stronger initial overshoot and a post-stimulus overshoot were observed. It was hypothesized from the time course analysis that the stronger initial overshoot reflected the activation of the SMA for motor control programming in the initial phase. Although the post-stimulus overshoot may be partially explained by cerebral blood flow (CBF) cerebral blood volume (CBV) uncoupling, its mechanism remained unknown. In the SM1, only the initial overshoot was observed and the level of BOLD signal was almost constant after the initial overshoot during the task period. These observations suggested that the BOLD signal is characterized by both CBF-CBV uncoupling and the neuronal activation characteristics in each region.

Adult↗
PubMed2000

Dissociation of writing processes: functional magnetic resonance imaging during writing of Japanese ideographic characters.

Dissociation between copying letters and writing to dictation has been reported in the clinical neuropsychological literature. Functional magnetic resonance imaging (fMRI) was conducted in normal volunteers to detect the neurofunctional differences between 'copying Kanji', the Japanese ideographic characters, and 'writing Kanji corresponding to phonological information'. Four tasks were conducted: the copying-Kanji task, the writing-Kanji-corresponding-to-phonogram task, the Kanji-grapheme-puzzle task, and the control task. The right superior parietal lobule was extensively activated during the copying-Kanji task (a model of the copying letters process) and the Kanji-grapheme-puzzle task. These observations suggested that this area was involved in referring the visual stimuli closely related to the ongoing handwriting movements. On the other hand, Broca's area, which is crucial for language production, was extensively activated during the writing-Kanji-corresponding-to-phonogram task (a model of the writing-to-dictation process). The Kanji-grapheme-puzzle task activated the bilateral border portions between the inferior parietal lobule and the occipital lobe, the left premotor area, and the bilateral supplementary motor area (SMA). Since the Kanji-grapheme-puzzle task involved manipulospatial characteristics, these results suggested cooperation between visuospatial and motor executive functions, which may be extensively utilized in demanding visual language processing. The neurofunctional difference between 'copying Kanji' and 'writing Kanji corresponding to phonogram' was efficiently demonstrated by this fMRI experiment.

Adult↗
PubMed2000

Evaluation of pancreatic islet cell tumors by fluorine-18 fluorodeoxyglucose positron emission tomography: comparison with other modalities.

PURPOSE: Pancreatic islet cell tumors are potentially malignant tumors and are often difficult to detect with current imaging modalities. Positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose (FDG) is an imaging technique with high sensitivity for malignant tumors. The aim of this study was to assess the feasibility of FDG PET to detect pancreatic islet cell tumors. METHODS: Nineteen lesions of histologically proved islet cell tumors were evaluated in 12 patients (5 men, 7 women; ages 22 to 77 years). FDG uptake was analyzed semiquantitatively as a standardized uptake value. The diagnostic accuracy of PET was compared with that of US, CT, and MRI. RESULTS: Of 19 lesions, 8 showed positive PET results (standardized uptake value > 2.3), and localization was indicated in 2 lesions. In nine tumors that were not detected by PET, seven were small tumors ranging from 1.5 to 8 mm in diameter and were not identified by other imaging methods. The sensitivity rate of PET was 53%, whereas those of US, CT, and MRI were 53%, 50%, and 53%, respectively. CONCLUSION: Our data suggest that FDG PET has a limitation in that it does not detect some small-sized islet cell tumors, mainly depending on their size, but it has potential utility as a complementary modality for other imaging techniques.

Adenoma, Islet Cell↗
PubMed2000

Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice.

Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated (131)I-labeled anti-CEA monoclonal antibody (MAb) (24 - 38 microg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72 - 115 microg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P < 0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P < 0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD.

Animals↗
PubMed2000

Perianal mucinous carcinoma successfully treated with a combination of external beam radiotherapy and high dose rate interstitial brachytherapy.

The case of an 84-year-old man with perianal mucinous carcinoma is presented. The tumour was 6 cm in diameter and extended into the surrounding tissues. Taking the patient's advanced age and disease into account, rectosigmoidectomy and colostomy were carried out without resection of most of the tumour. Radiotherapy consisted of pre-operative external beam radiotherapy (EBRT) of 40 Gy in 20 fractions, post-operative EBRT of 24 Gy in 12 fractions, and high dose rate interstitial brachytherapy of 12 Gy in a single fraction. The patient tolerated the entire course of radiotherapy well. The patient is doing well without regrowth or complications 7 years after radiotherapy. To our knowledge, there have been no reports on the successful outcome of radiotherapy for perianal mucinous carcinoma. This case suggests that a combination of EBRT plus interstitial brachytherapy boost may play a role in the definitive treatment of perianal mucinous carcinoma.

Adenocarcinoma, Mucinous↗
PubMed2000

Establishment and characterization of a breast cancer cell line expressing Na+/I- symporters for radioiodide concentrator gene therapy.

UNLABELLED: 131I therapy is a widely accepted treatment for metastatic differentiated thyroid cancer. To investigate the feasibility of 131I therapy for breast cancer, we established breast cancer cells stably expressing Na-/I- symporter (NIS) gene that can be modulated and studied in vitro and in vivo. METHODS: We transfected rat NIS genes into a human breast cancer cell line (MCF7) by electroporation. Iodide accumulation was evaluated under various extracellular concentrations of sodium and iodide, and iodide efflux was also assessed. Biodistribution and tumor imaging were studied using tumor-bearing mice. RESULTS: A novel cell line (MCF3B), stably expressing the NIS gene, was established from MCF7. MCF3B took up 44 times more radioiodide in vitro than MCF7 did. Iodide uptake was completely inhibited by 1 mmol/L perchlorate and was dependent on external sodium and iodide concentrations. Iodide efflux from MCF3B cells was slower (half-life [T 1/2] > 27 min) than from FRTL5 thyroid cells (T 1/2 = 4 min). In the biodistribution study using MCF3B-xenografted mice, high tumor uptake of 125I was shown (16.73%) at 1 h after injection, and tumor-to-normal tissue ratios were also high (4.84-21.28), except in the stomach (0.47). However, the iodide accumulation in the tumor lessened with time, reaching less than 1% at 24 h after injection. CONCLUSION: Our preliminary data indicate that NIS-based gene therapy may be applied by concentrating a lethal dose of radiation in tumor cells in vivo, but further investigation is necessary to determine a method of maintaining radioiodine in the cells to allow greater therapeutic effects.

Animals↗
PubMed2000

[Recent progress in radionuclide therapy].

Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.

3-Iodobenzylguanidine↗
PubMed1999

Avidin-biotin system for delivery of diagnostic agents.

Radiolabeled monoclonal antibodies specific for tumor-associated antigens are used for the diagnosis and therapy of malignant tumors. However, the blood clearance of antibodies is slow and tumor-to-nontumor ratios of radioactivity in the current system are not high. To increase tumor-to-nontumor ratios, the concept of pretargeting has been proposed. The strategy is based on the separate administration of the monoclonal antibody and the radiolabel. Because avidin and streptavidin bind to biotin selectively with extremely high affinity, the avidin-biotin system has been applied for pretargeting. With this method, high tumor-to-nontumor ratios are reported, not only in animal experiments, but also in clinical trials. The avidin-biotin system is also used to reduce the background radioactivity of the directly labeled antibody as well as radioimmunoguided surgery.

Journal Article↗
PubMed1999

Chemical design of radiolabeled antibody fragments for low renal radioactivity levels.

The renal uptake of radiolabeled antibody fragments presents a problem in targeted imaging and therapy. We hypothesized that the renal radioactivity levels of radiolabeled antibody fragments could be reduced if radiolabeled compounds of urinary excretion were released from glomerularly filtered antibody fragments before they were incorporated into renal cells by the action of brush border enzymes, present on the lumen of renal tubules. 3'-[131I]Iodohippuryl N(epsilon)-maleoyl-L-lysine ([131I]HML) was conjugated with a thiolated Fab fragment because the glycyl-lysine sequence in HML is a substrate for a brush border enzyme and metaiodohippuric acid is released by cleavage of the linkage. Fab fragments were also radiolabeled by direct radioiodination (125I-Fab) or by conjugation with meta-[125I]-iodohippuric acid via an amide bond [N-(5-maleimidopentyl) 3'-iodohippuric acid amide ([125I]MPH-Fab)] or an ester bond [maleimidoethy 3'-iodohippurate ([125I]MIH-Fab)] by procedures similar to those used for [131I]HML-Fab. In biodistribution experiments in mice, [131I]HML-Fab demonstrated markedly low renal radioactivity levels with kidney:blood ratios of radioactivity of 1 from 10 min to 1 h due to rapid release of meta-[131I]iodohippuric acid. [125]MIH-Fab and 1251-Fab reached their peak ratios of 3.8 and 7.3 at 1 h, respectively, and [125I]MPH-Fab showed the maximum ratio of 16.8 at 6 h. In subcellular distribution studies, both [125I]MIH-Fab and 125I-Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection, whereas the majority of the radioactivity was detected only in the membrane fraction after administration of [131I]HML-Fab at both time points. In nude mice, [131I]HML-Fab showed one-quarter of the renal radioactivity of simultaneously administered 125I-Fab without impairing the target radioactivity levels 3 h after injection. These findings indicated that HML is a useful reagent for targeted imaging and therapy using antibody fragments as vehicles. These findings also suggested that the radiochemical design of radiolabeled antibody fragments that liberate radiometabolites of urinary excretion from antibody fragments by the action of brush border enzymes may constitute a new strategy for reducing the renal radioactivity levels of antibody fragments.

Animals↗
PubMed1999

Contribution of PET in the detection of liver metastases from pancreatic tumours.

AIM: Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the liver is basically high, metastatic liver tumours are known to be positive on positron emission tomography (PET). The purpose of this study is to evaluate the diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic cancer. METHODS: Thirty-four patients with histologically proven malignant tumours of the pancreas underwent FDG-PET, computed tomography (CT) and transabdominal ultrasound (US). The findings of PET, CT and US were compared with the histopathologic findings at surgery or with clinical follow-up and the diagnostic accuracy of PET was evaluated. RESULTS: PET showed 28 regions of high FDG uptake (SUV = 3.3-9.1) in 13 patients. Twenty-six foci were metastatic lesions confirmed by surgery (n = 11), clinical follow-up (n = 10) or autopsy (n = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when the diagnosis by US or CT was unreliable because of the small size of the lesion. In two patients who had areas of high uptake in the liver, no metastases were detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients. Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a liver metastasis was found at surgery in one patient. The diagnostic accuracy of FDG-PET was 90%, which was comparable with that of US or CT. CONCLUSION: Our data suggest that PET is reliable in detecting liver, metastases from pancreatic cancer.

Adenocarcinoma↗
PubMed1999

Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody.

The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.

Animals↗
PubMed1999

A novel 111In-labeled antisense DNA probe with multi-chelating sites (MCS-probe) showing high specific radioactivity and labeling efficiency.

A multi-aminolinked oligodeoxynucleotide (ODN) was synthesized by substitution of dT with aminolinked dU in the sequence, following conjugation with isothiocyanobenzyl-EDTA (IBE) for 111In labeling. As a model target gene, the c-erbB-2 protooncogene was used. The probability of the number of aminolinked dU in the 20mer ODN was 5, but there were actually 3 and 4 in the selected antisense and sense ODNs, respectively. The IBE/ODN conjugation levels of probes with multi-chelating sites (MCS-probe) were 1.6 (antisense) and 2.4 (sense), more than 50 times higher than those of our previous studies using 5'-end aminolinked ODNs (IBE/ODN = 0.03). Labeling studies using the MCS-probe and 111In indicated that specific radioactivity as high as 48 MBq/nmol could be obtained with a labeling efficiency of over 90%. The 111In-antisense-MCS-probe could bound to sense ODN under physiological conditions, but the 111In-sense-MCA-probe could not. Thus, side-chain modification of ODN for metal labeling is considered to be useful for antisense techniques.

Antisense Elements (Genetics)↗
PubMed1999

A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment.

Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.

Angiotensin II↗
PubMed1999

Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland.

Elevation in serum human growth hormone (GH) level is known to be a factor that causes goiter development. The present study was designed to analyze sonographic and scintigraphic appearances of the thyroid in patients with acromegaly. The records of 48 consecutive patients with acromegaly were examined. Two patients had a history of operation for thyroid cancer. One had an atrophic thyroid gland after 131I treatment for Graves' disease. Goiter was palpable in 39 of the remaining 45 patients. Neither ultrasonography (US) nor scintigraphy was performed in 17 patients, including 6 with no palpable goiter and 11 with small diffuse goiter (group 1). Of the remaining 28 patients who underwent US, 14 had a moderately or markedly enlarged diffuse goiter (group 2), 13 were diagnosed as having adenomatous goiter (group 3), and 1 had a solitary cystic nodule. Among 11 patients in group 3 who underwent 123I or 99mTc thyroid scintigraphy, 6 showed uneven uptake, and 2 with undetectably reduced levels of thyrotropin (TSH) showed localized functioning areas. The mean serum TSH concentration in group 3 was significantly lower than that in group 1 or 2 (p<0.01). The duration of illness as acromegaly was significantly longer in group 2 and 3 as compared with group 1 (p<0.05). These results suggest that long-term stimulation by GH and insulin-like growth factor-I of thyroid follicular cells might be responsible for thyroid enlargement, presence of functioning lesions, slight overactivity of the thyroid, and the subsequent formation of multiple nodules in acromegalic patients. In conclusion, excluding two patients with thyroid cancer and one with Graves' disease, goiter was palpable in 39 of the 45 patients with acromegaly, among whom 14 (13 adenomatous goiters and 1 solitary cystic nodule) showed nodular enlargement.

Acromegaly↗
PubMed1999

Autoimmune pancreatitis with F-18 fluoro-2-deoxy-D-glucose PET findings

Two cases of pancreatitis induced by autoimmunity with PET images using F-18 fluoro-2-deoxy-D-glucose (FDG) are reported. The patients had abdominal pain and were thought to have possible pancreatic neoplasms. In one patient, PET showed intense uptake of the entire pancreas, but a Ga-67 scan yielded a negative result. Because the serum immunoglobulin G level was high, autoimmune pancreatitis was diagnosed in this patient. He underwent steroid therapy and fully recovered. In another patient with positive antinuclear antibodies and hyperglobulinemia, focal intense uptake was found in the head of the pancreas on the FDG PET. She also recovered with steroid therapy. Autoimmune pancreatitis is a relatively new form of chronic pancreatitis and should be kept in mind when making a differential diagnosis of pancreatic cancer with the assistance of FDG PET.

Journal Article↗