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Biomedical subjects

Y Akine

Publications and source records attributed to Y Akine.

At least 19 recordsLinked to original sources

Functional brain mapping of monkey tool use.

When using a tool, we can perceive a psychological association between the tool and the body parts-the tool is incorporated into our "body-image." During tool use, visual response properties of bimodal (tactile and visual) neurons in the intraparietal area of the monkey's cerebral cortex were modified to include the hand-held tool. Visual properties of the monkey intraparietal neurons may represent the body-image in the brain. We explored tool use-induced activation within the intraparietal area and elsewhere in alert monkey brain using positron emission tomography (PET). Tool use-related activities compared with the control condition (simple-stick manipulation) revealed a significant increase in cerebral blood flow in the corresponding intraparietal region, basal ganglia, presupplementary motor area, premotor cortex, and cerebellum. These tool use-specific areas may participate in maintaining and updating the body-image for the precise guidance of a hand-held rake onto a distant reward.

Animals↗

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging.

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.

Aged↗

Pharmacokinetic study of human natural beta-interferon in patients with end-stage renal failure.

AIMS: Although human natural beta-interferon (beta-IFN) is currently used in the treatment of a number diseases, there have been no published studies of the pharmacokinetics and pharmacodynamics of beta-IFN in patients with end-stage renal failure. MATERIALS: Five maintenance hemodialysis patients with chronic hepatitis C (4 men and 1 woman) were enrolled in this study. METHODS: For the pharmacokinetic study, blood samples were obtained from a forearm vein at intervals, before infusion and 0, 3, 5, 10, 20, 30, and 40 minutes after a 15-minute intravenous infusion of human natural beta-IFN (Feron, Toray Industries, Inc., Tokyo) at a dose of 600 MIU. RESULTS: Intravenous beta-IFN was administrated safely to all five patients. The plasma half-life of beta-IFN was found to be 6.91 +/- 2.80 (mean +/- SD) minutes. The initial volume of distribution was found to be 0.49 +/- 0.02 l/kg. CONCLUSION: A 15-minute intravenous infusion of human natural beta-IFN was safely administered to the hemodialysis patients. This pharmacokinetic study showed that it is not necessary to reduce the dosage in patients with end-stage renal failure.

Alanine Transaminase↗

Comparison of radiation effects of gadolinium and boron neutron capture reactions.

PURPOSE: Cell survival assays were performed to evaluate the effects of radiations released during neutron capture reactions by gadolinium-157, boron-10 and by the combination of both. MATERIALS AND METHODS: Single cell suspensions with or without Gd-157 and/or B-10 were exposed to thermal neutrons produced by the Kyoto University reactor, and standard cell survival curves were obtained. RESULTS: Under the same molarity, cytocidal effects were 1.5 times greater for Gd-157 than for boron when compared at 10% survival levels. The presence of B-10 enhanced the radiation effect of Gd-157 neutron capture by 1.2-fold, suggesting that cells were not sufficiently irradiated as a result of neutron fluency attenuation by the presence of excess neutron capture agents in the medium. CONCLUSIONS: When an equal number of atoms were present, Gd-157 was effective as B-10 when exposed to an equal number of thermal neutrons. However, there was no benefit observed in the combination of Gd-157 and B-10 for neutron capture therapy. Further studies are needed to determine optimal Gd-157 and B-10 concentrations as a function of tumor dimension.

Animals↗

Changes in the liver parenchyma after proton beam radiotherapy: evaluation with MR imaging.

The objective of this study was to describe magnetic resonance (MR) findings with a 1.5T imager for hepatic parenchymal changes after proton beam radiotherapy. Thirty-two patients who received proton radiotherapy with doses of 50-87 Gy underwent MR imaging 1-75 months (mean 22 months) after the start of irradiation. Axial T(2), T(1)-weighted imaging, and a dynamic study after a gadolinium injection were performed. The irradiated areas showed hypointense in T(1)-weighted images, hyperintense in T(2)-weighted images, and intense and prolonged enhancement on the dynamic study (maximum relative enhancement 441.8%+/-263.3 vs. surrounding liver 145.6%+/-67.7, p<0.0001). T(2) values of the irradiated areas were 50.6 to 65.8 msec greater than in the surrounding liver (p<0.005). The values increased with time, being significantly greater 13 months or longer after the beginning of the therapy than after a period of less than 3 months (p<0.05). Pathologic examinations (n = 3) indicated that the irradiated areas were composed of collapsed lobules with hepatic small vein occlusions, and rich extracellular matrices which retained extracellular fluid. MR imaging can demonstrate hepatic parenchymal changes after proton beam radiotherapy, and show the changes are irreversible.

Adult↗

Long-term observations of a patient with choroidal melanoma following fractionated stereotactic radiotherapy: a case report.

A 60-year-old man with choroidal melanoma was treated with fractionated stereotactic radiotherapy and followed for 6 years. During this period, the tumor has not changed in size, and the patient has experienced only a slight decrease in visual acuity. In this case, stereotactic radiotherapy appears to have been safe and effective and may also be a cost-effective alternative to particle or plaque therapy.

Choroid Neoplasms↗

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer: a prospective study.

BACKGROUND: A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. METHODS: Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. Intra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. RESULTS: Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. CONCLUSIONS: This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function.

Aged↗

Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions.

Transcription factor GATA-2 is essential for the proper function of hematopoietic stem cells and progenitors. Two first exons/promoters have been found in the mouse GATA-2 gene, and a distal IS promoter shows activity specific to hematopoietic progenitors and neural tissues. To ascertain whether the two-promoter system is also utilized in the human GATA-2 gene, we isolated and analyzed a P1 phage clone containing this gene. The nucleotide sequence of the human GATA-2 gene 5' flanking region was determined over 10 kbp, and a human IS exon was identified in the locus through sequence comparison analysis with that of the mouse GATA-2 IS exon. RNA blotting and reverse-transcribed PCR analyses identified a transcript that starts from the IS exon in human leukemia-derived cell lines. The IS-originated transcript was also identified in CD34-positive bone marrow and cord blood mononuclear cells, which are recognized as clinically important hematopoietic stem cell-enriched fractions. Phylogenic comparison of the human and mouse GATA-2 gene sequences revealed several regions in the locus that exhibit high sequence similarity. These results demonstrate that the GATA-2 gene regulatory machinery is conserved among vertebrates. The fact that the human IS promoter is active in the hematopoietic stem cell/progenitor fraction may be an important clue for the design of a vector system that can specifically express various genes in hematopoietic stem cells and progenitors.

Animals↗

Multi-layer energy filter for realizing conformal irradiation in charged particle therapy.

A new type of filter for charged particle radiotherapy is developed to reduce unwanted dose transfer to the normal tissues around a tumor. The new filter can make a static irradiation field where the width of the spread-out Bragg peak (SOBP) is two-dimensionally adjusted. That makes the field conformal to the tumor three-dimensionally. The filter is made of many layers produced by using stereolithography. The layer has a miniaturized structure that has geometrical similarity to the conventional ridge filter. Shapes of cone and pyramid are also usable for the unit-cell constructing the layer. The spread of the field in the depth direction is decided by the thickness of the filter, or by the number of layers. The experimental result of the irradiation using the ridge-type construction shows a good agreement with an estimate by the Monte Carlo calculation. By combining this technique with intensity modulation that has lateral position dependence, the conformal irradiation can be achieved by a simple procedure.

Equipment Design↗

Preservation of hypervascularity in hepatocellular carcinoma after effective proton-beam radiotherapy--CT observation.

AIM: The aim of this study was to describe persistence of hypervascularity in proton treated hepatocellular carcinoma at serial follow-up computed tomography (CT). METHODS: Four patients with unresectable solitary hypervascular hepatocellular carcinoma underwent 55-82 Gy proton-beam irradiation for a period of 15-47 days. Follow-up CT including plain, enhanced and dynamic imaging was performed for a period of 9-36 months. RESULTS: Good preservation of arterial blood supply while gradual decrease in tumour size was clearly depicted by dynamic CT. CONCLUSION: We believe that preservation of hypervascularity as judged by enhancement at CT and magnetic resonance imaging, does not necessarily mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.

Aged↗

Biodistribution of gadolinium incorporated in lipid emulsions intraperitoneally administered for neutron-capture therapy with tumor-bearing hamsters.

Emulsions containing a distearylamide (Gd-DTPA-SA) or a distearylester (Gd-DTPA-SE) of Gd (gadolinium)-diethylenetriaminepentaacetic acid (Gd-DTPA) were intraperitoneally injected in Greene's melanoma-bearing hamsters at a dose of 2.0 ml (3.0 or 6.0 mg Gd) per hamster. In the standard-Gd and high-Gd formulations used, the weight ratios of soybean oil, water, Gd-DTPA derivative (Gd-DTPA-SA or Gd-DTPA-SE), hydrogenated L-alpha-phosphatidylcholine from egg yolk (HEPC) and co-surfactant (HCO-60, Myrj 53, Myrj 59 or Brij 700) were 7.36:92:1:2:3 and 7.36:92:2:1:3, respectively. When the effects of the co-surfactants on the biodistribution of Gd from Gd-DTPA-SA-containing emulsions in the standard-Gd formulation were compared, the HCO-60 emulsion exhibited the highest Gd accumulation in tumors, possibly resulting from its fast and complete absorption, its small particle size (78 nm) and the stable coat on the particle surfaces with polyoxyethylene. Brij 700 emulsion kept the highest blood Gd concentration for a prolonged period, possibly due to particle properties similar to those of HCO-60. However, it exhibited a slower Gd accumulation in tumors, only reaching an identical level, in comparison with the HCO-60 emulsion. This suggested the tumor to be saturated with lipid particles. When Gd-DTPA-SE was used instead of Gd-DTPA-SA, its HCO-60 emulsion exhibited only very poor Gd-accumulation due to its easy degradation. The HCO-60 emulsion particles containing Gd-DTPA-SA in the high-Gd formulation (6.0 mg Gd in 2 ml) exhibited in vivo behavior identical to those in the standard-Gd formulation; then the Gd level in tumors reached 107 micrograms Gd/g tumor (wet), and the tumor:blood (T/B) and tumor:skin (T/Sk) Gd concentration ratios were 13.2 and 5.6, respectively, at 48 h after intraperitoneal administration. These results suggest that when intraperitoneally administered, this HCO-60 emulsion, and possibly also the corresponding Brij 700 emulsion, may be an excellent delivery system for accumulating Gd in tumors in neutron-capture therapy (NCT).

Animals↗

Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy.

Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.

Animals↗

Fractionated stereotactic radiotherapy of small intracranial malignancies.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.

Analysis of Variance↗

Reirradiation of brain and skull base tumors with fractionated stereotactic radiotherapy.

PURPOSE: We evaluated the feasibility of fractionated stereotactic radiotherapy for small intracranial recurrences after conventional radiotherapy. METHODS AND MATERIALS: Nineteen patients who had initially undergone conventional radiotherapy to intracranial lesions, receiving a median total dose of 50 Gy in 5 weeks, were retreated with stereotactic radiotherapy for their recurrences and received a median total dose of 42 Gy in seven fractions over 2.3 weeks. RESULTS: Of the 19 patients, 15 achieved local control 3-51 months after reirradiation. No patient suffered from acute reaction, but one patient with a history of extensive radiotherapy developed progressive radionecrosis 9 months after reirradiation. CONCLUSIONS: Fractionated stereotactic radiotherapy of intracranial recurrences appears to be effective in achieving in local control with negligible morbidity. We believe it merits further investigation in a prospective study.

Adult↗

Radiation tolerance of cirrhotic livers in relation to the preserved functional capacity: analysis of patients with hepatocellular carcinoma treated by focused proton beam radiotherapy.

PURPOSE: To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy. MATERIALS AND METHODS: We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12-27 months after proton beam radiotherapy. Tumors were treated with focused proton beams with target doses of 140-186 TDF (time, dose, and fractionation). We measured the degree of hypertrophy of the untreated liver volume by measuring the total liver volume and the treated liver volume which was radiologically identified on contrast-enhanced CT scans. The risk of radiation-induced liver failure was estimated using the prediction score (PS) originally used for estimating posthepatectomy liver failure, substituting the planned treated liver volume for the resection liver volume. RESULTS: The degree of hypertrophy ranged from -19% to 51%, and was significantly positively correlated with the ratio of the planned treated liver volume to the functional liver volume. The PS agreed well with observed radiation tolerance in 21 patients, but underestimated the tolerance in 5. This underestimation was diminished when the PS was recalculated using the identified untreated liver volume in lieu of the planned untreated liver volume. CONCLUSION: As in surgical treatment, radiation tolerance of the cirrhotic liver after focused treatment is closely related to the preserved functional capacity of the identified untreated liver volume, which shows compensatory hypertrophy following radiotherapy.

Aged↗

Fractionated stereotactic radiotherapy for choroidal melanoma.

Stereotactic radiotherapy used for the treatment of choroidal melanoma made use of a 6-MeV linac with built-in multileaf collimators and a simple plastic head mold. The latter provided excellent head and ocular immobilization. The system resulted in highly localized dose distributions with a maximum 2-mm targeting error during fractionated treatments. Based on these techniques, sixteen patients with choroidal melanoma have so far been treated. Majority of patients received a total dose of 48 Gy in 8 fractions. Fourteen patients who presented with small- to moderate-sized tumors have remained free of relapse or major complications during the follow-up period of 3-42 months. Two patients who presented with an extensive tumor eventually required enucleation after irradiation. Technical precision required for stereotactic radiotherapy and reproducibility for fractionation appear adequate. Encouraging preliminary results justify further studies to evaluate its efficacy as an alternative to other conventional therapeutic approaches.

Adult↗