Search

Nosocomial infections acquired during the course of cardiac surgery and hospitalization can have devastating patient consequences. The source of these infections is often difficult to determine which complicates eradication efforts. Recently it has become apparent that the heater-cooler devices used in conjunction with cardiopulmonary bypass may become contaminated with bacteria that are normally found in hospital water sources. The culprit organisms are nontuberculous mycobacteria which coat the intrinsic surfaces found within the circuits of the heater-coolers. Aerosolization of the bacteria occurs during normal heater-cooler operation which can disperse the organisms throughout the operating room. The bacteria are slow-growing and may not present for months, or years, following exposure which makes epidemiological determination a challenge. The ensuing report summarizes a recent outbreak in these infections that have been reported both in Europe and the United States, along with efforts to reduce the risk for patient infection.

We developed an effective hemostatic method using Hydrofit® and a hemostatic gelatin sponge (Spongel®). We evaluated the hemostatic effect in comparison to the conventional silicone sheet method. A simulated circuit was created using the pump of a Nipro ventricular assist system and a prosthetic graft. A hole was made in the graft by a needle and three hemostatic methods were applied: the silicone sheet method (SS) using Hydrofit® and a silicone sheet, the bread and butter method (BB) using Hydrofit® and a gelatin sponge instead of a silicone sheet, and French toast method (FT) using Hydrofit® and a gelatin sponge over which water was poured before compression. The amount of leakage before and after the application each of the methods was measured according to the compression time. In the 60 s compression, the amount of leakage after SS, BB, and FT was 0.4 ± 0.8, 0.2 ± 0.6, and 0 ± 0.0 ml, respectively, and FT showed no leakage. In the 30 s compression, the amount of leakage after SS, BB, and FT was 14.2 ± 27.9, 1.0 ± 3.2, and 7.8 ± 22.6 ml, respectively, and did not differ to a statistically significant extent. The method of combining Hydrofit® and Spongel® could obtain reliable hemostasis in 60 s.

We developed a surgical hemostatic film using Hydrofit® (Hydrofit® film). This film is prepared by reacting Hydrofit® with water in advance, and it can be used in the same way as an accessory silicone sheet. In addition, unlike the silicone sheet, there is no need to remove the Hydrofit® film from the body. In the present study, we describe the hemostatic effect of our new method using Hydrofit® film. We created a pulsatile flow circuit model using a ventricular assist device and a vascular graft. The circuit was filled with water, and the systolic pressure was adjusted to ≥ 130 mmHg. The artificial blood vessel was punctured by an 18-G needle. Operations to prevent water from leaking were attempted through either a conventional method using a silicone sheet or our new method using Hydrofit® film. In the 180-s trial, 14 attempts (93.3%) with the Hydrofit® film were successful. In the silicone sheet group, 13 attempts (86.7%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in 10 (66.5%) cases after the silicone sheet was removed. After short-duration hemostasis for 60 s, good waterproofing was obtained in the Hydrofit® film group (success in 17 cases [85%]). In contrast, in the silicone sheet group, 10 attempts (50%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in only 7 (35%) cases after the silicone sheet was removed. Hydrofit® film showed good hemostatic performance in the pulsatile flow circuit model.

Egg white protein has a high net protein utilisation, with a score of 100 in the amino acid rating system. Although the enzymatic breakdown of egg white yields hydrolysates that are rapidly absorbed and various physiological activities can be expected from them, flavouring egg white to meet taste requirements as a food has been a difficult challenge. Herein, we developed a high-molecular-weight egg white hydrolysate and compared the absorption rate and nutritional value of the hydrolysate with those of egg white proteins obtained from raw materials, whey proteins, and hydrolysates, also known as high-quality proteins. The absorption rate of egg white hydrolysates was faster than that of egg white and whey proteins in portal vein cannulated rats, and their bioavailability values were higher than those of whey proteins and hydrolysates. According to the protein digestibility-corrected amino acid score and digestible indispensable amino acid score, the scores for egg white hydrolysates were equivalent to those of egg white and whey proteins but higher than those of whey hydrolysates. Our results show that egg white hydrolysates maintain the nutritional value of egg whites and are rapidly absorbed by the body.

We developed an effective hemostatic method using HydrofitA simulated circuit was created using the pump of a Nipro ventricular assist system and a prosthetic graft. A hole was made in the graft by a needle and three hemostatic methods were applied: the silicone sheet method (SS) using HydrofitIn the 60 s compression, the amount of leakage after SS, BB, and FT was 0.4 ± 0.8, 0.2 ± 0.6, and 0 ± 0.0 ml, respectively, and FT showed no leakage. In the 30 s compression, the amount of leakage after SS, BB, and FT was 14.2 ± 27.9, 1.0 ± 3.2, and 7.8 ± 22.6 ml, respectively, and did not differ to a statistically significant extent.The method of combining Hydrofit

We developed a surgical hemostatic film using Hydrofit

Frozen cooked pasta meals are offered to meet the increasing demand for high-quality pasta products with ready-to-eat convenience. However, textural changes during freezing and after thawing may consequently modify pasta quality, which requires strategies to minimize texture deterioration. Two egg white powders (EWP), namely, P110 and M200 from Henningsen Foods, Inc. were incorporated at different levels (0, 3 and 5 g/100 g semolina flour) into cooked and frozen wheat semolina pasta to improve their texture and cooking quality. The water absorption of pasta was greatly improved, while the cooking loss was significantly reduced by EWP. The negative effect of freezing and reheating processes on the pasta texture could be significantly minimized by EWP, especially M200 at 3 g/100 g semolina flour. The dynamic rheology on pasta dough and total sulfhydryl and disulfide in two egg white solutions were measured. It can be seen that M200 could form a stronger gel-like structure than P110, which may contribute to significant free sulfhydryl/disulfide exchange with gluten. It could be seen that the findings in this work demonstrated the potential of using EWP especially M200 to improve fresh and frozen pasta texture and quality.

Human LECT2 is a 16-kDa chemotactic protein that consists of 133 amino acids and three intramolecular disulfide bonds. Here, we present the oxidative refolding of (His)(6)-LECT2, an N-terminally (His)(6)-tagged recombinant protein of human LECT2. (His)(6)-LECT2 was overproduced in Escherichia coli in the form of insoluble aggregates, solubilized with 8 M urea in the presence of 10 mM DTT, and purified and refolded on Ni-NTA agarose by lowering the urea concentration before the elution. This process, however, gave a mixture of oligomers of (His)(6)-LECT2 as well as the monomer, whose composition was as low as 36%. The oligomers formed as a result of incorrect intermolecular disulfide bonds. After the refolding on Ni-NTA agarose (step 1), the disulfide bonds were shuffled using a glutathione redox buffer (step 2) and the remaining thiols were completely oxidized (step 3) to improve the yield of correctly folded, monomeric (His)(6)-LECT2. The monomer composition was significantly improved to 81% by the three-step refolding method and the monomer thus obtained was shown to have the same conformation as the authentic LECT2 produced in CHO cells by CD and NMR spectroscopies. The yield of (His)(6)-LECT2 was 1.0 mg/L E. coli culture and was 16 times as high as that in our previous report, in which (His)(6)-LECT2 was purified from the soluble fractions of E. coli cell lysates.

A 57-year-old male presented with a rare case of spontaneous vertebral arteriovenous fistula manifesting as radiculopathy of the right arm, subsequently associated with pulsating tinnitus and vascular bruit in the nape. He had a past history of chiropractic-induced vertebrobasilar infarction. Angiography showed a simple and direct fistula between the third segment of the right vertebral artery and the epidural veins at the C-1 level, where the artery runs backward above the arch of the C-1 just proximal to the penetration of the dura. The fistula was successfully obliterated by coil embolization, resulting in rapid improvement of the signs and symptoms. Mechanical compression to the nerve roots by the engorged epidural veins with arterial pressure was considered to be the major cause of radiculopathy. Vertebral artery dissection induced by chiropractic manipulation is most likely responsible for the development of the fistula.

A 68-year-old male presented an unusual dural arteriovenous fistula (AVF) located at the craniocervical junction. Magnetic resonance imaging revealed dilated perimedullary veins around the spinal cord at C-1 and C-2 levels, as well as high intensity signals in the spinal cord on T2-weighted images. Vertebral angiography identified an AVF at the point where the right vertebral artery penetrates the dura. The fistula was a single and direct communication between the vertebral artery and the spinal vein. Surgical interruption of the fistula at its venous side resulted in prompt improvement of both motor and sensory signs and symptoms.

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the blood content in parenchyma. These values allow for BNCT, using thermal neutrons, on brain tumors located less than approximately 3.3 cm in depth from the brain surface of neutron incidence, providing that the dose on the normal endothelium is controlled to less than the tolerance limit. In our preliminary study of BNCT, a 31% 3-year survival was achieved over all for 16 glioblastoma patients and a 50% 2-year survival was achieved on 8 glioblastoma patients in our recent dose escalation study based on these data.

Bioactive bone cement (BABC) is a novel artificial bone cement. It has some noteworthy characteristics that are applicable to neurological surgery. The toxicity of BABC to the nervous system was tested by implanting BABC and polymethylmethacrylate (PMMA) cement as a control at the parietal and the suboccipital regions of the skull in beagles. The auditory brainstem response (ABR) was tested before and after implantation. Sections of the cerebral cortex and the acoustic nerve were examined at 3 and 6 months after implantation. No abnormal ABR was found in any animals. Histological examination of the cerebral cortex and acoustic nerve demonstrated slight gliosis in both the BABC and PMMA cement groups, but no other abnormalities.

Several studies have shown that selenium can inhibit tumorigenesis in tissues. However, little is known about the mechanism and the effect of selenium on DNA, especially in brain tumor cells. In this study we examined the biological effect of selenium on human glioma cell lines (A172 and T98G). Selenium exhibited an antiproliferative effect on these cell lines (and induced the typical ladder pattern of DNA fragmentation commonly found in apoptosis), which were prevented by catalase. Few effects of selenium on NT14 fibroblasts were found. These findings demonstrate that selenium may induce, by apoptosis, cell death of human glioma cell lines, which are resulting from free radical oxygen forming.

Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

A 45-year-old male presented with sudden onset of severe headache, mild disorientation, and gait disturbance due to intracystic hemorrhage from a cerebellar hemangioblastoma. He was successfully treated with ventricular drainage followed by total removal of the tumor. Reported cases of intracranial hemangioblastoma with massive hemorrhage show male predominance, tend to be solid rather than cystic, and occur in supratentorial more than infratentorial locations. Thin-walled and dilated vessels in the present and other cases were a possible cause of hemorrhage. Massive hemorrhage from hemangioblastoma is rare but needs prompt treatment because of the relatively high mortality.

Purpose: The association between the cerebrospinal fluid cytology findings and the clinical features of patients with intracranial germinoma was investigated to determine whether cerebrospinal fluid cytology could be helpful in determining the optimal radiation treatment volume. Methods and Materials: Between 1976 and 1992, cerebrospinal fluid cytology was performed in 42 germinoma patients using a cytocentrifugation method. Forty patients received irradiation and 2 received chemotherapy with cisplatin and etoposide. Results: Cerebrospinal fluid cytology was positive in 22 of the 42 patients (52%). Dissemination via cerebrospinal fluid (intraventricular or spinal) was present at the initial diagnosis in eight (36%) of the 22 cytology-positive patients and none of the 20 negative patients. After treatment, cerebrospinal fluid dissemination developed in four (18%) of the cytology-positive patients and one (5%) of the negative patients. Two of the former four patients had received chemotherapy alone as initial treatment. Five patients with positive cytology received irradiation to a smaller volume than the cerebrospinal axis (primary tumor site plus spinal axis in three and whole brain in two), but they have not developed recurrence in the 4 to 14 years since therapy. The 5-year survival rate was 93% for the cytology-positive patients and 94% for the negative patients. Conclusion: Cerebrospinal fluid cytology-positive patients have a higher risk of cerebrospinal fluid dissemination and it seems reasonable to give them low-dose (20–24 Gy) prophylactic craniospinal irradiation. When properly irradiated, the prognosis of cytology-positive patients is as good as that of negative patients.

IL-5 synergies with IL-2 to produce increased LAK activity, although IL-5 alone induced little cytotoxic activity. The most dramatic synergy occurred with a suboptimal IL-2 concentration. The kinetics of LAK activity induced by IL-2 plus IL-5 were similar to those induced by IL-2. IL-5 exerted its effects during the late stage of IL-2 induced LAK generation. In the precursor phase, depletion of asialo-GM1+ cells preceding culture eliminated IL-2 plus IL-5 induced LAK activity. In the effector phase, IL-2 plus IL-5 induced LAK activity was eliminated by depletion of Thy1.2+ cells following culture.

A murine monoclonal antibody 3H3 recognizes the basic fibroblast growth factor (FGF) and inhibits the growth of human glioblastoma cells both in vitro and in vivo. We studied the potential of a scintigraphic technique using the 3H3 antibody to detect tumors that produce basic FGF. 125I- and 111In-labeled 3H3 bound to U87MG human glioblastoma cells in vitro. U87MG cells were inoculated subcutaneously into nude mice. After development of the tumor, radiolabeled 3H3 was injected into the subcutaneous space surrounding the tumor. A high level of radioactivity from 3H3 was retained at the tumor, whereas an irrelevant antibody cleared rapidly from the injected site. Radiolabeled 3H3 was not retained in tumors that did not produce basic FGF. Scintigraphic detection of tumors expressing basic FGF would be valuable for the therapeutic application of the antibody.

We have examined the immunoregulatory effect of local and continuous secretion of interleukin 7 (IL-7) from murine glioma cells (203-glioma) engineered by murine IL-7 gene transfection. Secretion of IL-7 from glioma cells did not result in morphology or growth rate changes but did reduce tumorigenicity in vivo in proportion to the amount of IL-7 produced. This reduction in tumorigenicity could be reversed in a dose-dependent fashion by injection of anti-IL-7 neutralizing monoclonal antibody at the tumor site. Mice immunized with IL-7-producing glioma cells showed a specific immune response to 203-glioma but not to two other syngeneic cell lines (B-16, a melanoma, and YM-12, a fibrosarcoma). IL-7-producing glioma cells were not rejected in mice depleted of CD8+ cells but were rejected in mice depleted of CD4+ or NK1.1+ cells. These results suggest that CD8+ T cells may play an important role in tumor rejection.

Tyrosine-specific phosphorylated proteins found exclusively on the cell surface of human astrocytomas were previously identified with murine monoclonal antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to further characterize the antigens and investigate the relationship between them and c-kit protooncogene product. We demonstrated that the antigens had protein kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the membrane of A172 human glioblastoma cells.

A 60-year-old male and a 36-year-old female suffered shunt migration after lumboperitoneal shunt procedures, upward into the spinal subarachnoid space and downward into the abdominal cavity, respectively. Defects of the fixation devices in the shunt system are considered the main cause in both cases. Upward migration of the lumbar tube in the subarachnoid space is extremely rare. We suppose that raised abdominal pressure is related to this unusual complication.

Two tightly linked recombination activating genes, RAG-1 and RAG-2, are involved in VDJ recombination of the immune system. Although these genes were originally thought to be expressed exclusively in precursor B and T cells, RAG-1 transcripts were recently found in the murine central nervous system (CNS) [Chun et al., Cell 6, 189, (1991)]. We found that the RAG-2 gene was expressed in CNS tumor cell lines, melanoma (B-16) and skin fibroblast (A9). RAG-1 expression was not found in any non-lymphoid cell lines examined including CNS tumor cell lines. Another VDJ recombination-related gene RBP-Jk was expressed in all tumor cell lines examined. It remains to be seen whether expression of RAG-1 and RAG-2 in CNS is abortive or functionally important.

We report here that a neutralizing mouse monoclonal antibody against basic FGF inhibited both anchorage-dependent and anchorage-independent growth of U-87MG and T98G human glioblastoma cells and HeLa cells, all of which express both the basic FGF and the FGF remptor genes. In addition, the subcutaneous administration of this antibody significantly suppressed the tumor development or these tumor cells in nude mice. Therefore, basic FGF plays an important role in neoplastic growth of these cells. The neutralization or basic FGF will be effective in controlling the growth of tumors, such as glioblastoma and other cancer cells which bear basic FGF and FGF receptors.

The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was significant. In contrast, transforming growth factor type beta 1 was expressed in all the samples investigated. The mRNA for basic FGF and its peptide were localized in tumor cells in vivo by in situ hybridization and immunohistochemistry, showing that basic FGF is actually produced in tumor cells. Our results suggest that tumor-derived basic FGF is involved in the progression of gliomas and meningiomas in vivo, whereas acidic FGF is expressed in a tumor origin-specific manner, suggesting that acidic FGF works in tandem with basic FGF in glioma tumorigenesis.

The clonal analysis in the ultrastructure of tumor-lymphocyte interaction was carried out in order to investigate the precise mechanism responsible for CTL-mediated cytolysis of tumor cells. A glioma-derived cell line (GI-1) and autologous tumor-specific cytotoxic T lymphocyte (CTL) clones were established. The CTL lines were composed of the morphologically homogeneous lymphocytes with intracytoplasmic electron-dense secretory granules. After the stimulation by GI-1, the size of the CTLs increased, and the intracytoplasmic organellas were developed. It was noted that the intracytoplasmic secretory granules markedly increased in number and size, and many of them exhibited an “immature” appearance. On the other hand, the tumor cells underwent a progressive degeneration. In contrast, the stimulation by other antigens caused only small morphological changes in the CTLs. It is suggested, therefore, that the secretory function of tumor-specific CTLs is activated by the stimulation of the specific antigen, and that soluble factors in the secretory granules in the CTLs may be closely associated with the mechanism of target Cell lysis.

Since 1990, we have treated fourteen glioblastoma patients by BNCT using BSH according to Hatanaka’s procedures. However, in our early patients, who were almost all advanced cases, good clinical results were not obtained, probably because the tumor to blood ratio of 10B concentration in our BNCT subjects was always under 1 and/or around lOppm, respectively, considerably lower than the expected values. In our recent subjects, assuming the T/B ratio to be 1.0, the 10B concentration in blood was maintained at around 30ppm during BNCT to achieve a 10B concentration in the tumor of 28ppm, the theoretically required minimum concentration. This strategy improved the post-BNCT course in glioblastoma patients. In both glioblastoma patients and brain tumor animals models, the T/B ratio of BSH has been reported to show wide variations (l, 2, 3). To estimate the optimal dosage of BSH, we have previously investigated the quantitative distribution of BSH in tumors and blood in newly diagnosed subjects and in brain tumor-bearing animals. In this study, we investigated the quantitative distribution of BSH via prompt gamma ray spectroscopy (PGS) and an α-track etch method (ATM) in newly diagnosed human glioblastoma patients and its effectiveness was discussed for the clinical purpose.

We have conjugated a positron tracer F-18 to [10B]boronophenylalanine (10B-BPA) to synthesize [18F]fluoroboronophenylalanine (18F-10B-DL-BPA or 18F-10B-L-BPA), and analyzed 1013-BPA metabolism on 27 cases of the various brain tumors by positron emission tomography (PET). These PET data revealed that 18F-10B-BPA using the DL-form was actively incorporated to the malignant tumor cells, showing high B-10 concentration and T/N ratio, which was suggested of the sufficient effectiveness of boron neutron capture therapy (BNCT) on the malignant brain tumor. The experimental studies were undertaken with rat glioma model which showed that BNCT using 10B-L-BPA brought the good antitumor effect on rat glioma and no side effect on normal brain. Under this PET-BNCT system, the patient with malignant brain tumor was treated.

Mutations of the p53 gene are found in various human cancers. The frequency of its mutation is reported to increase during tumor progression in most tumors. In human gliomas, mutations of the p53 gene are found in about one-third of the malignant forms and in few of the benign ones, indicating their possible involvement in tumor progression. On the other hand, we have recently shown that basic fibroblast growth factor (basic FGF) plays a crucial role in tumor progression as an autocrine growth factor in tissues of human gliomas. Therefore, we hypothesized that p53 might regulate the promoter activity of the basic FGF gene, which has several GC boxes and no typical TATA box. In this study, cotransfection assays using human glioblastoma and hepatocellular carcinoma cells and establishment of stable cell lines expressing mutant-type p53 were performed. The basic FGF gene promoter was demonstrated to be regulated by p53 at the transcriptional level and its basal core promoter was found to be responsive to p53. Expression of endogenous basic FGF was also demonstrated to be activated by mutant type p53. Wild-type p53 repressed gene expression of the basic FGF and its mutant activated it in vitro, implying one of the possible pathways in tumor progression.

We studied the effect that treating two types of glioblastoma cell lines, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their susceptibility to lysis by lymphokine-activated killer (LAK) cells. We also examined the participation of cell-adhesion molecules and major histocompatibility complex (MHC) class I and II antigens present on the target cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml) for 48 hours resulted in the increased expression of both intercellular-adhesion molecule 1 and MHC class I antigens on tumor cells. In addition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affected by IFN-gamma treatment. These changes in expression were accompanied by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further inhibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-gamma increased their susceptibility to lysis by LAK cells. These findings suggest that treatment of glioblastoma cells with IFN-gamma decreased their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expression of MHC class I antigen on target cells.

In order to investigate the clinical significance of glucose consumption (GC) in recurrent gliomas, positron emission tomography with 18F-labeled fluorodeoxyglucose was measured in 18 cases of histologically verified recurrent gliomas. The GC of the tumors were categorized into four groups. Five tumors were in Group IV, the highest GC, four were in Group III, eight were in Group II, and one was in Group I. Masses in Groups III and IV were clearly defined as a hot spot higher than or similar to the GC of the contralateral cortex. Half of the recurrent gliomas showed the lower GC of Group I or II, but two thirds of these were histologically high-grade gliomas. Although GC in the recurrent gliomas did not always increase as expected, a focal increase of GC, even mild and small, in the area of previous surgery is diagnostically important. Tumors with high GC showed high histological malignancy, irrespective of tissue damage. Patients with tumors of low GC had longer survival rates than those with high GC, although statistical significance was not obtained. Thus, positron emission tomography with 18F-labeled fluorodeoxyglucose was useful for detecting the recurrence of gliomas and suggesting their histological malignancy and prognosis. Care should be taken because viable tumor cells could be present in areas of low GC and small recurrent masses could be missed because of the poor spatial resolution of positron emission tomography.

In supratentorial low-grade astrocytoma, radiation therapy effects and prognostic factors, especially with respect to computed tomography (CT) findings, are not yet well established. A retrospective analysis of 119 patients with this disease (histologically confirmed ordinary astrocytoma) therefore was conducted.Between 1965 and 1989, 101 patients received postoperative radiation therapy, whereas 18 patients received surgery alone. Radiation was directed to the tumor plus a 1- to 3-cm margin in almost all cases; the dose range was 41 to 66 Gy (mean, 57 Gy). CT scan was performed before treatment on 74 patients. Postoperative survival rates were compared by both univariate and multivariate analyses.The 5- and 10-year survival rates for the irradiated group were 60% and 41%, respectively, which were significantly better than those for the surgery-alone group (37% and 11%, P = 0.048). Among various potential prognostic factors for the irradiated patients, only a lower age was associated with a better prognosis. Sex, tumor site (deep-seated or not), extent of surgery, radiation dose and field, and adjuvant chemotherapy did not influence the prognosis significantly. Among various CT findings, a clear tumor margin, a maximum tumor area less than 25 cm2, presence of a cyst, and lack of mass effect were associated with a better prognosis on univariate analysis (P = 0.02-0.12), but contrast enhancement was not related to prognosis. On multivariate analysis, however, mass effect was the only significant factor.Radiation therapy appears definitely to be effective in improving the prognosis for low-grade astrocytoma. Younger age, and the absence of mass effect determined by CT, were associated significantly with a better prognosis.

Twenty-four patients, 19 with brain tumors and 5 with malignant melanomas, have been treated at the Kyoto University Reactor by boron neutron capture therapy (BNCT) in the past two years. The purpose of this paper is to summarize the seven cases we treated and to examine the most suitable conditions for patients, boron compounds, and irradiation modification for successful BNCT.

A case of treatment-related leukoencephalopathy is presented. A patient with medulloblastoma was postoperatively treated with craniospinal axis irradiation. One month after irradiation, weekly intrathecal administration of methotrexate was performed 4 times to treat cerebrospinal fluid dissemination of the tumor. Two months after the initiation of intrathecal chemotherapy, the patient became somnolent and developed decerebrate posturing. Magnetic resonance imaging showed diffuse leukoencephalopathy. Positron emission tomography revealed a diffuse decrease in glucose uptake in the deep white matter. Auditory evoked potential also showed diffuse abnormalities, not only in the cerebrum, but also in the brain stem. High dose intravenous leucovorin rescue was attempted without any neurologic improvement.

The mechanism by which interferon gamma (IFN-gamma) decreases the susceptibility of the established cultured gliosarcoma line Gl-1 to lymphokine-activated killer (LAK) lysis was analyzed. The results of monolayer depletion and lectin-dependent cellular cytotoxicity assays by LAK cells revealed that the resistance to LAK lysis of IFN-gamma-treated Gl-1 cells is manifested at the stage of LAK cell target recognition alone. We have also divided LAK cells into populations of phenotypically natural killer (NK)- and T-like cells with monoclonal antibodies and complement, respectively. We have used these cells to examine the mechanism of IFN-gamma-induced protection of Gl-1 cells from LAK lysis in cold target inhibition, monolayer depletion, and direct binding assays. The results revealed that NK-like cells do not recognize IFN-gamma-treated Gl-1 cells as efficiently as they do untreated targets, whereas T-like cells show the opposite tendency. In conclusion, we have demonstrated that the IFN-gamma induced protection of tumor cells from LAK lysis is predominantly regulated by the target recognition of NK-like cells. On the other hand, IFN-gamma-treated tumor cells may bind to T-like cells but fail to trigger them to initiate further stages for lysis as effectively as NK-like cells.

Three murine monoclonal antibodies, designated GA-17, GB-4, and GC-3, were prepared by the hybridization of murine myeloma cells (NS-1) and spleen cells of BALB/c mice immunized with the crude membrane fraction of cultured human gliosarcoma cells (GI-1). Two of them (GA-17 and GB-4) reacted exclusively with the membrane of glioma cells, and the other (GC-3) reacted with the membrane of glioma cells and a T cell line (MOLT-4). Although these antibodies reacted with almost all of the gliomas, the reactions differed. GA-17 reacted equally well with all glioblastoma (17 cases) and low-grade astrocytoma (10 cases), whereas GB-4 reacted poorly with 7 cases of glioblastoma and GC-3 did not react with 7 cases of low-grade astrocytoma. The antigens, exclusively expressed on the cell surface, were analyzed by surface labeling with 125I followed by a cell lysis and immunoprecipitation with these antibodies. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GA-17, GB-4, and GC-3 reacted with Mr 140,000-145,000, Mr 160,000, and Mr 145,000-150,000 proteins, respectively. Some evidence has been obtained indicating that these antigens are composed of the same polypeptide chain (Mr 120,000) with the carbohydrate chains being different.

A permanent cell line, GI-1, was established from a human gliosarcoma, and its characteristics were investigated. The original tumor was a mixture of two different neoplasms which had components of both glioma and sarcoma. The established cell line expressed various mesenchymal antigens, but not neuroepithelial antigens. It was noted, however, that the cell line produced tumors with the morphological features of human glioma after inoculation in athymic mice. The contrast of the pathological characteristics in tissue culture and in xenograft was unique, and this finding suggests that the GI-1 cell line may have the features of both glioma and sarcoma.

Boron Neutron Capture Therapy (B-NCT) has been successfuly reported during this quarter century (1). In this therapy, boron accumulation into neoplastic tissue must be attained. Gadolinium has been proposed as an another potential nuclide of NCT (2,3,4). Gd-157 has an approximately 64 times greater thermal neutron cross section, 255,000barns, than Boron-l0, and the neutron capture reaction releases a total kinetic energy of 7.94MeV shared amongst prompt γ - rays, internal conversion electrons and Auger electrons (5). The long range high energy γ - rays and electrons can deliver appreciable doses to infiltrating neoplastic satellite lesions of the tumor (3). Also Gd-DTPA, which is an enhancement material for MR imaging, is clinically available as a tumor seeking agent(6). In this study the tumorcidal effect of Gd-NCT was investigated using Gd-DTPA, and its killing effect was confirmed in in-vitro and in-vivo systems.

The research nuclear reactor of Kyoto University (KUR), which was established in 1963, has the power of 5 MW and has rendered services to scientists in various fields including biology and medicine. The first clinical application was carried out on a brain tumour patient by Professor Hatanaka in 1974. Ten patients were treated from 1987 to January of 1991. As no medical doctor had served in the KUR Institute and clinical facilities were not available, there were no treatments from 1975 to 1986. After two medical doctors arrived at their posts in the Institute, KUR opened its door for clinical activities again in 1987.

Northern blot analysis showed transcripts of two types of the fibroblast growth factor (FGF) receptor genes, flg and bek, in almost all the tissues samples of 18 human gliomas and 22 human meningiomas, which produced abundant basic and/or acidic FGF. From immunohistochemistry, FGF receptors were expressed in the tumor cells of a glioma and a meningioma. RNA expression of these FGF receptors was also detectable in normal human brains and normal bovine meninges. The expression level of either FGF receptor gene was not significantly different between tumor tissues and normal tissues.

The success of Boron Neutron Capture Therapy (B-NCT) has been reported for the last 25 years. [1]. This therapy requires boron to accumulate into neoplastic tissue. Gadolinium (Gd) has been proposed as an another potential nuclide for NCT [2–4] because Gd-157 has an approximately 64-fold greater thermal neutron cross-section (255,000 barns), than does Boron-10, and releases a large total kinetic energy (7.94 MeV) which it shares among prompt γ-rays, internal conversion electrons, and Auger electrons by the thermal neutron capture reaction [5]. Long ranges of high energy γ-rays and electrons deliver doses to infiltrating neoplastic satellite lesions of the main tumor [3]. Additionally, Gd-DTPA, an enhanced material for MR imaging, is clinically available as a tumor-seeking agent. In this study the tumoricidal effect of Gd-NCT was investigated using Gd-DTPA, and its killing effect was confirmed in in vitro and in vivo systems.