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Biomedical subjects

O Aizawa

Publications and source records attributed to O Aizawa.

At least 19 recordsLinked to original sources

Homotypic adhesion through carcinoembryonic antigen plays a role in hepatic metastasis development.

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 microg/ml) LS-LM4 cells under a Ca2+-free condition as compared with the control (P<0.01). Anti-CEA antibody (100 microg/ml) inhibited cell aggregation under a Ca2+-free condition (P<0.05). Treatment with anti-E-cadherin antibody (60 microg/ml) plus anti-CEA antibody (100 microg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca2+. In vivo, there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group (P<0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control (P<0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA.

Animals

The requirements and development of neutron beams for neutron capture therapy of brain cancer.

One of the two overriding conditions for successful BNCT is that there must be a sufficient number of thermal neutrons delivered to each of the boronated cells in the tumour bed (target volume). Despite the poor experience with BNCT in the USA some 40 years ago, the continued apparent success of BNCT in Japan since 1968, lead indirectly to the re-start of clinical trials on BNCT in 1994 at both Brookhaven and MIT. Similar trials will start soon at Petten in Europe. At other centres worldwide, many neutron beam designs are being proposed with either thermal or epithermal neutrons, emanating predominantly from nuclear research reactors. It is apparent that whilst the success of BNCT depends on a suitable neutron beam, there is a diversity in available designs, as well as each proposed type of neutron source, with consequently different characteristics of the emergent neutron beam. The paper presents the historical development of neutron beams used for BNCT, addresses the requirements on the types of beams, describes some of the existing designs and other proposals elsewhere and lastly, considers the broader requirements in designing NCT facilities. The focus of the paper is on treatment of brain cancer, neutron beam requirements for other types of cancer may vary.

Boron Neutron Capture Therapy

Vasospastic angina in a patient with Fabry's disease who showed normal coronary angiographic findings.

It has been reported that coronary diseases in patients with Fabry's disease are induced by deposits in endothelial cells and coronary smooth muscle cells. Most of those are ischemia due to stenosis. This report describes a case of patient with Fabry's disease who showed severe vasospasms without coronary artery stenosis during acetylcholine loaded coronary angiography. In this case, a myocardial biopsy revealed that the deposits in the endothelial cells of the myocardial capillaries were lamellated appearance. Recently, it is reported that endothelial cell damage could be an important cause of coronary vasospasm. This case suggests that the some sort of functional disorder was induced by glyco-sphingolipid deposits in the coronary endothelial cells, and that this might have led to coronary artery spasms without the organic stenosis of coronary arteries.

Adult

Influence of cisapride on the pharmacokinetics and antihypertensive effect of sustained-release nifedipine.

To investigate the clinical significance of interactions between cisapride and sustained-release nifedipine, we compared the plasma nifedipine concentration and blood pressure after administration of nifedipine alone (20 mg) with those obtained after administration of nifedipine cisapride (2.5 mg) in 20 patients with hypertension. The plasma nifedipine level was not altered by cisapride at one hour after administration, but was significantly increased at two (p < 0.01), three (p < 0.01), and four (p < 0.05) hours when compared with the level measured after nifedipine alone. Cisapride significantly decreased the mean blood pressure at three hours (p < 0.05) after administration of nifedipine. The acetaminophen method was used to determine gastric emptying time. The plasma concentration of acetaminophen at 45 minutes after administration was significantly increased by cisapride, suggesting that enhanced gastrointestinal motility might be the basis for the increase in the plasma nifedipine concentration. These results suggest that enhancement of the antihypertensive effect of nifedipine can occur when the drug is prescribed with cisapride, and that caution is needed when using such a combination therapy.

Aged

Evaluation of neutron irradiation field for boron neutron capture therapy by using absorbed dose in a phantom.

PURPOSE: The method of an evaluation for the dose characteristics of BNCT is presented, and an eccentric core design for the TRIGA-II reactor is proposed. METHODS AND MATERIALS: We have defined the "irradiation time" as the time of irradiation in which the "maximum 1 microgram/g dose" becomes 3,000 RBE-cGy, because we assumed that the normal tissue contained 1 microgram/g 10B. We have also changed the RBE values and calculated the absorbed dose in the "irradiation time" by using an arrangement including both a facility structure and a body phantom. Moreover, we have modified the dose criteria for BNCT as follows: The "eye dose," "total body dose," and "except-head dose" should be less than 200, 100, and 50 RBE-cGy, respectively. We have added one more criteria for BNCT-that the thermal neutron fluence at the tumor position (5 cm from the surface) should be over 2.5 x 10(12) n/cm2 in the "irradiation time." RESULTS: The distance from the core side to the irradiation port is a very important factor to design a neutron irradiation field for BNCT. CONCLUSION: We can get the acceptable dose for BNCT with only 1-h irradiation by using a 100 kW reactor if we can get the irradiation port at the distance of 120 cm from the core side.

Boron Neutron Capture Therapy

A case of toxic megacolon in ulcerative colitis associated with cytomegalovirus infection.

Cytomegalovirus (CMV) infection, which has been shown to complicate the course of ulcerative colitis (UC), has been implicated as a possible etiologic factor in the exacerbation of UC, especially in toxic megacolon. However, CMV infection in patients with UC accompanied by toxic megacolon has rarely been reported. Here we report a case of CMV infection of the colon accompanied by toxic megacolon occurring in UC. A 38-year-old woman had been treated with intravenous hydrocortisone, rectal steroid, and central venous alimentation for 6 weeks under the diagnosis of UC. She was transferred to Akita University Hospital because of increasing bloody diarrhea and abdominal pain. Toxic megacolon was identified by examinations on admission, and she underwent a total colectomy. Examination of the surgical specimen showed severe inflammation of the colon. Microscopically, cytomegalic inclusions were observed in and around the endothelial cells in the inflamed submucosal layer. It can be assumed that CMV infection was a secondary, opportunistic invader superimposed on UC, and that it played an important role in altering the clinical course of the patient.

Adult

The size of regional lymph nodes does not correlate with the presence or absence of metastasis in lymph nodes in rectal cancer.

We evaluated the relationship between the size of regional lymph nodes and the presence of metastasis in them in rectal cancer. Of 1,064 lymph nodes in 46 specimens, 133 (13%) were found to have metastases. A half of the positive nodes and most of the negative ones were less than 5 mm in diameter. Therefore, we must find lymph nodes smaller than 5 mm in diameter for assessment of lymph node metastasis. Although positive nodes were larger than negative ones, there was no significant difference. However, when comparing the size of lymph nodes in relation to their location, the epi- and pararectal lymph nodes larger than 10 mm in diameter were highly suggestive of metastases, but the size of the lymph node was not a reliable indicator of lymph node metastases in other situations.

Humans

The clinical significance of regional variations in histologic differentiation within carcinomas of the colorectum.

The clinical significance of the presence or absence of regional variations in histologic differentiation within a primary colorectal carcinoma was investigated in this study. Regional variations in histologic differentiation were judged to be present when the low power field of a microscope was occupied by cancer tissue cytologically and architecturally different from that of the surrounding area. Regional variations in histologic differentiation were noted in 153 (42%) of 368 primary carcinomas. Carcinomas with regional variations were of an anaplastic histologic type and had a higher incidence of lymph node metastasis and a worse prognosis than those without regional variations. Thus, the histologic diversity within a carcinoma is thought to be important for determining the prognosis of patients with colorectal cancer.

Adenocarcinoma

Phantom experiment and calculation for in vivo 10boron analysis by prompt gamma ray spectroscopy.

In order to determine 10B concentrations in a tumour in vivo without injuring tissues, phantom experiments and calculations were carried out for boron neutron capture therapy. The experiment was based on prompt gamma ray spectroscopy and a single-crystal silicon-filtered neutron beam from a TRIGA-II reactor. Calibration curves to determine the 10B concentrations in the tumours were experimentally generated from known 10B values for simulated tumours with various volumes in a phantom. The 10B distributions in a tumour were also investigated and it was possible to distinguish the tumour with 10B from normal tissue without 10B. In addition, the 10B concentrations were estimated by calculations. A two-dimensional discrete ordinate transport code, DOT3.5, was employed for the calculations of the neutron fluence rate distributions in a phantom. The number of incidental gamma rays entering a germanium detector, which were produced in a tumour as a result of neutron reaction, were calculated by an analytical method. The results were in good agreement with the experiments.

Boron

Prompt gamma-ray neutron activation analysis of boron-10 in biological materials.

Prompt gamma-ray neutron activation analysis of 10B concentrations in biological samples was carried out using a germanium detector and single crystal silicon filtered neutron beams from the TRIGA-II reactor. The 10B concentrations of biological samples such as tumors, tissues, blood and cultured cells were estimated from calibration curves obtained by using standard samples containing various 10B concentrations. A method of measuring absolute 10B concentrations was also presented.

Boron

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.

Animals

Head phantom experiment and calculation for boron neutron capture therapy.

Head phantom experiments with various neutron beams and calculations were carried out in order to provide useful information for boron neutron capture therapy (BNCT). Thermal neutron beams for thermal neutron capture therapy were used for phantom experiments with various neutron collimator aperture sizes. The filtered beam neutrons of 24 and 144 keV generated with iron and silicon filters were also used to investigate the possible application of BNCT in the treatment of deep-seated cancers. Thermal neutron fluence and induced capture gamma dose distributions within the phantom were calculated with a transport code DOT 3.5 and compared with the experimental results. The results showed that the calculation used was consistent with the experimental results and provided useful information on BNCT. The filtered beam neutron may be very useful for the treatment of deep or widespread cancer, if there were a high power research reactor constructed for this purpose.

Brain Neoplasms

[Coronary artery blood flow velocity non-invasively measured using a vessel-tracking pulsed Doppler system].

A newly-developed noninvasive method was used to measure left coronary blood flow during phantom experiments. Two techniques were used in which: (1) the sample position can always be set in a fluctuating vessel using a wall echo-tracking method with a phase-locked-loop, and (2) the Doppler reference signal was generated separately synchronous with the wall echo signal. These techniques were combined, using a commercially available pulsed Doppler apparatus (SSH-40B: Toshiba). Basic experiments were performed using a blood vessel phantom to verify the validity of these systems. Blood flow velocity in the fluctuating tube could be measured clearly using a vessel-tracking method. The blood flow velocity of the left anterior descending artery was measured in three normal subjects and in seven patients from the third intercostal space along the left sternal border. The velocity pattern was characterized by a crescendo-decrescendo shape in diastole. The peak velocity which appeared in diastole ranged from 19 to 69 cm/sec, with no difference by disease entity. However, in all cases, the blood flow velocity signals were marred by extraneous signals, making it impossible to measure blood flow velocity during systole. Further improvement of the system is mandatory in order to use this flowmeter clinically.

Adult

Depth-dose evaluation and optimisation of the irradiation facility for boron neutron capture therapy of brain tumours.

Boron neutron capture therapy (BNCT) of brain tumours was investigated using thermal neutrons generated by a middle-power research reactor such as the TRIGA-II. The spatial distributions of neutrons and gamma rays were measured using a head phantom at different collimator apertures. Total depth-dose distributions were deduced from these results and were evaluated. We also obtained an optimum condition in terms of the collimator aperture, the 10B concentration in the tumour and the ratio of 10B concentration in the tumour to that in normal tissue. We found that, under this condition, BNCT using thermal neutrons from the TRIGA-II could be successfully used to treat a deep tumour.

Boron