Dependence of fructooligosaccharide content on activity of fructooligosaccharide-metabolizing enzymes in yacon (Smallanthus sonchifolius) tuberous roots during storage.

Tuberous roots of yacon (Smallanthus sonchifolius) accumulate about 10%, on a fresh weight basis, of inulin-type fructooligosacharides (FOSs), known as a food ingredient with various healthy benefits. However, we have a great difficulty to ensure these benefits because FOSs with a lower degree of polymerization (DP) decreased remarkably, and fructose increased when the tuberous roots were stored after harvesting even under previously recommended storage conditions of low temperature with high humidity. In the present study, to elucidate the involvement of FOS-metabolizing enzymes in FOS reduction during storage at 90% relative humidity and 8 degrees C, we extracted a crude protein from yacon tuberous roots and measured the activities of invertase (beta-fructofuranosidase, EC 3.2.1.26), sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99), fructan:fructan 1-fructosyltransferase (1-FFT, EC 2.4.1.100), and fructan 1-exohydrolase (1-FEH, EC 3.2.1.80). The enzyme activities acting on sucrose, both invertase and 1-SST, were weakened after storage for a month. In addition, the activity of 1-FEH acting on short FOSs such as 1-kestose (GF(2)) and 1-nystose (GF(3)) was higher than that of 1-FFT. These results suggest that the continuous decline in FOSs of low DP during storage was dependent mainly on the 1-FEH activity. On the other hand, FOSs with a DP of >or= 9 only slightly decreased in stored yacon tuberous roots during storage, though distinct 1-FEH activity was observed in vitro toward a high-DP inulin-type substrate, indicating that highly polymerized FOSs content was unlikely to be closely connected with the 1-FEH activity.

[Clinical evaluation of "Takotsubo" cardiomyopathy with 123I-MIBG myocardial scintigraphy: a case report].

We report a case of "Takotsubo" cardiomyopathy that was considered to be caused by hypercatecholaminemia due to mental stress. Myocardial scintigraphy using 123I-MIBG revealed severe damage to the myocardial sympathetic nerve terminals at the site of reduced left ventricular wall motion on left ventriculography. In this case, cardiac nuclear imaging with 123I-MIBG appeared to be useful for understanding the pathophysiology when combined with ECG and left ventriculography.

Whole-body hybrid PET with 18F-FDG in the staging of non-Hodgkin's lymphoma.

UNLABELLED: PET with a double-head gamma camera (hybrid PET) is a new approach to tumor imaging with 18F-FDG. This study was conducted to clarify the feasibility of whole-body FDG hybrid PET in the staging of non-Hodgkin's lymphoma (NHL) in comparison with PET with a dedicated camera (dedicated PET) and to compare the results of both FDG studies with those of CT and 67Ga scanning as conventional imaging studies (CIS). METHODS: Thirty patients with NHL were prospectively evaluated. The results of the imaging studies regarding detection of the sites involved and staging were compared with each other and with those of the reference standard based on the final overall clinical evaluation. RESULTS: Of the total of 206 sites, whole-body FDG hybrid PET and dedicated PET detected 159 sites (77.2%) and 179 sites (86.9%), respectively. Eighteen of the 20 sites missed by hybrid PET alone consisted of lesions < 1.5 cm. Both FDG studies provided concordant staging results in all but 2 patients. CIS, on the other hand, detected 164 (79.6%) of the 206 sites, 137 of which were also detected by hybrid PET. Hybrid PET detected an additional 22 sites not found by CIS, whereas CIS detected 27 additional sites. Hybrid PET and CIS provided concordant staging results in 19 patients. Hybrid PET correctly staged NHL in 5 additional patients, whereas CIS correctly staged NHL in only 1 additional patient. CONCLUSION: Whole-body FDG hybrid PET appeared to be an accurate method of staging NHL. Despite its poorer image quality compared with dedicated PET, hybrid PET provided NHL staging results comparable with those of dedicated PET. Hybrid PET also yielded results comparable with those of CIS. However, whole-body FDG hybrid PET is currently inadequate as a single modality for staging NHL and is complementary to CT.

Serial changes in 14C-deoxyglucose and 201Tl uptake in autoimmune myocarditis in rats.

UNLABELLED: This study was designed to examine the relationships between the uptake of 14C-deoxyglucose (DG) and the uptake of 201Tl in a rat model of autoimmune myocarditis. METHODS: Autoimmune myocarditis was induced in normal rats by immunization with pig cardiac myosin. Dual-tracer autoradiography with DG and 201Tl was performed on frozen slices of the animals' hearts 3 wk (acute phase), 8 wk (subacute phase), and 14 wk (chronic phase) (each n = 5) after immunization. The extent of inflammatory damage was classified histologically into three categories on the basis of cell infiltration: mild (Mi), moderate (Mo), and severe (Sv). The regional count in the region of interest set on the autoradiogram was normalized on the basis of that of control rats. The ratio of total cardiac uptake to the injected dose (%ID/g x BW, where ID is injected dose and BW is body weight) was calculated by tissue counting. Expressions of glucose transporters GLUT1 and 4 were evaluated by the enzyme-labeled antibody method. RESULTS: The total cardiac uptake of DG in the acute phase of myocarditis was significantly higher than in normal control rats (3.43% +/- 0.92% vs. 0.97% +/- 0.38%; P < 0.0001); it then decreased in the chronic phase but was still higher than in the controls (1.85% +/- 0.37% vs. 0.97% +/- 0.38%; P < 0.01). The total cardiac uptake of 201Tl in the acute phase of myocarditis was significantly lower than in the controls (7.4% +/- 0.7% vs. 12.0% +/- 3.3%; P < 0.005); it then increased in the chronic phase and reached normal levels (13.0% +/- 3.3% vs. 12.0% +/- 3.3%; not significant [NS]). In the acute phase, the regional uptakes of DG in the Mi, Mo, and Sv regions were 143.1% +/- 107.9%, 169.6% +/- 59.9%, and 317.5% +/- 103.3%, respectively, whereas those of 201Tl were 88.4% +/- 31.9%, 72.1% +/- 34.6%, and 48.4% +/- 21.5%, respectively. GLUT expression was evaluated visually and classified into four grades (0, 1, 2, and 3). In the acute phase, GLUT1 expression was higher in rats in the Sv group than in the controls (2.87 vs. 0.87). GLUT4 was not expressed in the Sv areas but was found in the Mi areas. CONCLUSION: In the acute phase of autoimmune myocarditis in rats, cardiac uptake of DG was accelerated by severe inflammation. Cardiac uptake of 201Tl, on the other hand, was suppressed. Our results suggest that GLUT1 expression accelerates DG uptake by cells in areas of severe inflammation.

Fluorine-18 FDG myocardial positron emission tomographic findings before and after pituitary adenoma resection in a patient with acromegalic cardiomyopathy.

Because of persistently elevated growth hormone levels, acromegaly gives rise to various changes in organs mediated by insulin-like growth factor-I. In the heart, it causes myocardial hypertrophy, and, with time, heart failure. The authors performed pituitary adenomectomy in a patient with acromegalic cardiomyopathy who had heart failure; after operation, the blood growth hormone levels decreased to within the normal range and there was a marked improvement in left ventricular function by gated blood pool scintigraphy. Pre- and postoperative fluorine-18 fluorodeoxyglucose (FDG) myocardial positron emission tomography showed increased accumulation of FDG in the myocardium before surgery, but accumulation within the normal range after operation. Myocardial glucose metabolism changed when the long-term effects of growth hormone and insulin-like growth factor-I were eliminated, and this appears to be accurately reflected by FDG positron emission tomography.

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.

Left ventricular volumes and ejection fraction calculated from quantitative electrocardiographic-gated 99mTc-tetrofosmin myocardial SPECT.

UNLABELLED: We compared the left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) as calculated by Cedars automated quantitative gated SPECT (QGS) to those determined by first-pass radionuclide angiography (FPRNA) and contrast left ventriculography (LVG) in a group of 21 patients (mean age 61.4 +/- 9.2 y). METHODS: A total of 740 MBq 99mTc-tetrofosmin was administered rapidly into the right cubital vein at rest, and FPRNA was performed using a multicrystal gamma camera. One hour after injection, QGS was performed with a temporal resolution of 10 frames per R-R interval. LVG was performed within 2 wk. RESULTS: The EDV, ESV and LVEF calculated by QGS were highly reproducible (intraobserver, r = 0.99, r = 0.99 and r = 0.99, respectively; interobserver, r = 0.99, r = 0.99 and r = 0.99, respectively; P < 0.01) and were more consistent than those determined by FPRNA (intraobserver, r = 0.97, r = 0.95 and r = 0.93, respectively; interobserver, r = 0.86, r = 0.96 and r = 0.91, respectively; P < 0.01). There was a good correlation between EDV, ESV and LVEF by FPRNA and those by LVG (r = 0.61, r = 0.72 and r = 0.91, respectively; P < 0.01), and there was an excellent correlation between QGS and LVG (r = 0.73, r = 0.83 and r = 0.87, respectively; P < 0.01). The mean EDV by QGS (100 +/- 11.3 mL) was significantly lower than by FPRNA (132 +/- 16.8 mL) or LVG (130 +/- 8.1 mL), and the mean ESV by QGS (53.8 +/- 9.3 mL) was lower than by FPRNA (73.0 +/- 13.3 mL). Ejection fraction values were highest by LVG (57.1% +/- 3.2%), then QGS (51.8% +/- 3.0%) and FPRNA (48.9% +/- 2.4%). CONCLUSION: QGS gave more reproducible results than FPRNA. LV volumes and LVEF calculated by QGS correlated well to those by LVG.

Exercise-induced stunning continues for at least one hour: evaluation with quantitative gated single-photon emission tomography.

To elucidate the after-effect of exercise on left ventricular (LV) function, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were evaluated at 1 h after exercise and at rest by technetium-99m tetrofosmin gated myocardial single-photon emission tomography (SPET) using an automated program in 53 subjects. The subjects were grouped as follows: normal scan (n = 16), ischaemia (n = 19) and infarction (n = 18), based on the interpretation of perfusion images. Postexercise LVEF did not differ from resting LVEF in the groups with normal scan and infarction. In patients with ischaemia, postexercise EDV (90+/-17 ml, mean +/-SD) and ESV (44+/-15 ml) were significantly higher than EDV (84+/-15 ml, P = 0.001) and ESV (36+/-14 ml, P<0.0005) at rest. LVEF was significantly depressed 1 h after exercise (53%+/-9% vs 58%+/-9%, P<0.0001). In ischaemic patients with depressed postexercise LVEF, LVEF difference between rest and postexercise showed a significant correlation with the sum of defect scores, which were reversible from exercise to rest perfusion images (r = 0.92, P<0.0001). These results indicate that exercise-induced LV dysfunction (myocardial stunning) continues for at least 1 h in ischaemic patients and that the extent of LVEF depression is determined by the severity of ischaemia.

[Three patients with Gilbert's syndrome associated with constitutional excretory defect of indocyanine green].

We routinely perform, as a preoperative liver function test, the indocyanin green (ICG) test in patients scheduled for operations under general anesthesia. Doubts have been raised, however, concerning the necessity for this test, since no abnormalities have ever been detected by it. Nonetheless, we noted a high level of ICG retention and a slight increase in indirect bilirubin in 3 patients, and further investigation led to a diagnosis of Gilbert's syndrome accompanied by constitutional impairment of ICG excretion. This syndrome can be associated with perioperative jaundice in patients with malnutrition and those who received halothane, morphine, or some other agents. Although the indirect bilirubin level increased briefly after surgery, no other abnormalities occurred in the 3 patients. Since this syndrome is asymptomatic and is detected incidentally, the preoperative ICG test was considered to be useful.

Case report: hepatocellular carcinoma diagnosed radiologically, treated by transcatheter arterial embolization and limited-field radiotherapy.

Even though the resection rate for hepatocellular carcinoma (HCC) has risen recently, many patients cannot be treated surgically because of the advanced stage of the tumour and/or coexisting cirrhosis. An alternative therapeutic approach for some of these patients is transcatheter arterial embolization (TAE) which has become very common in Japan. However, it is not a curative measure, and an additional therapy is required to eradicate the residual disease. In this communication, we report a case in which a patient with HCC has been successfully treated by TAE followed by limited-field radiotherapy. The results suggest that this is a very promising therapeutic approach for HCC and that the potential of limited-field radiotherapy for HCC with or without TAE also needs to be explored.

Suppression of rabbit VX-2 subcutaneous tumor growth by gadolinium neutron capture therapy.

VX-2 tumors growing in hind legs of New Zealand White rabbits (n = 4) were exposed to thermal neutrons for 40 min (2.1 x 10(12) neutrons cm-2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5-6 fold higher than that in the contralateral tumor. Growth of gadolinium-infused tumors was significantly inhibited compared to that of control tumors (P < 0.05) between the 16th and 23rd days after treatment.

Design and preparation of ethyl cellulose microcapsules of gadopentetate dimeglumine for neutron-capture therapy using the Wurster process.

Microcapsules of hygroscopic, highly water-soluble gadopentetate dimeglumine (Gd-DTPA-DM) for use in preliminary in vivo experiments for neutron-capture therapy were designed. They were prepared with such properties as a particle size small enough to be suspended and injected through a syringe, a negligible release of Gd-DTPA-DM, and a high drug content by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 microm, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP), a drug-layer of Gd-DTPA-DM, EC and PVP, a waterproof coat and a release-sustaining overcoat of EC and cholesterol (1:1), and a surface treated with hydrogenated egg lecithin. By curing at 110 degrees C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 microm microcapsules to less than 10% for the first 20 min, which was the period required to prepare a suspension, inject it and irradiate the neutron. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy.

Electron-equivalent dose for the effect of gadolinium neutron capture therapy on the growth of subcutaneously-inoculated Ehrlich tumor cells in mice.

The present in vivo study estimates the dose resulting from the gadolinium neutron capture reaction and the gadolinium enhancement extent of the thermal neutron effect. The assay is based on the time required from cell inoculation to the formation of tumors with an arbitrary size of 200 mm2. Mice were inoculated subcutaneously with Ehrlich tumor cells with or without meglumine gadopentetate (1.2 mg 157Gd/0.2 ml), and were exposed to 1.1 x 10(12) thermal neutrons cm-2(n 8), or 3 MeV electrons at three dose levels (each n 10). To reach 200 mm2 in size, it took 18.8 days for tumors treated with neutrons only and 34.7 days for those treated with gadolinium and neutrons. From the time-dose relation obtained with 3 MeV electrons, the equivalent doses corresponding to delays of 34.7 and 18.8 days were 15.0 and 7.4 Gy, respectively. Thus, gadolinium enhanced the thermal neutron effect two-fold (15.0/7.4) in the present study.

Linac-based small-field radiotherapy for brain tumors.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 mm. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8-14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Analyses of distant metastases in squamous cell carcinoma of the head and neck and lesions above the clavicle at autopsy.

The frequency of distant metastases was studied in 112 patients who had squamous cell carcinoma of the head and neck. All of these patients died of the tumor and underwent postmortem examinations. Forty-one (37%) of the 112 patients had distant metastases at the time of death. There was a significant correlation between development of distant metastases and the presence of cervical nodes. Of the patients who had distant metastases, 63% had evidence of tumor in the cervical nodes, whereas 37% of these patients were free of disease in the neck. Patients with residual or recurrent tumors in the cervical nodes had a high risk of distant metastases.

Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules.

Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.

Radiotherapy of T1 glottic cancer with 6 MeV X rays.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities: a retrospective analysis of 244 patients.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.

Radiation effect of gadolinium-neutron capture reactions on the survival of Chinese hamster cells.

In gadolinium-neutron capture reactions, prompt gamma rays with an energy spectrum of up to 7 MeV, X-rays and electrons are released. We measured the effect of radiation as a result of capture reactions on cultured Chinese hamster cells. Cells in the medium containing 5000 ppm gadolinium were exposed to thermal neutrons from a nuclear reactor. The survival curve for those cells exhibited a shoulder in the low neutron fluence region. The survival curve for cells exposed to thermal neutrons in the absence of gadolinium was a simple exponential function. To obtain 10% survival levels, 5.4 x 10(12) neutrons/cm2 were required for cells irradiated in the absence of gadolinium, and 1.55 x 10(12) neutrons/cm2 for those irradiated in the presence of gadolinium. The therapeutic ratio in gadolinium-neutron capture therapy depends on the difference in 157Gd concentrations between the tumor and normal tissues. Thus, our current effort has been to develop a method of selectively delivering 157Gd to tumors.