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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Alumina ceramic (Bioceram®) is an excellent material that is stable in and compatible with biological tissues, though harder and more fragile than antogenous bone. Recently, new ceramics have been developed for the purpose of overcoming the disadvantages of alumina ceramics. For example, zirconia ceramics have almost the same flexural strength as iron and hydroxy apatite consists of the same molecular elements as autogenous bone. Tissue compatibilities and radiological properties of three ceramics were investigated. First, tissue culture dishes (30 mm in diameter and 5 mm in depth) were made of the three ceramics and the adherence of cultured tumor cells to these dishes at 37°C for 90 minutes were compared with glass dishes and plastic culture dishes (Nunclon®). There was no difference in adherence between alumina ceramics and zirconia ceramics, both of which are superior to hydroxy apatite. Next, the growth rate for 1 week of cultured tumor cells on the ceramic dishes were examined. There were no differences between the three ceramics with regard to doubling time, while the growth rate on alumina ceramics exceeded that of the other ceramics. Thirdly, ceramic pieces were implanted in the parietal bone of mongrel dogs and histological changes, especially new bone formation, were investigated. Tongue-like exostosis of new bone along the ceramic piece was observed 2 months after implantation of alumina ceramic and 3 months for zirconia ceramic. Tissue reaction was slight. Finally, the artifacts of each ceramic on computerized tomography (CT) scan image were investigated. In the application of ceramics to neurosurgical field, artifacts on CT scan are an obstacle. Alumina ceramic showed minimum artifact on CT scan. Alumina ceramic is considered to be the most suitable material among the three ceramics in the neurosurgical field at present.

Two types of “spontaneous” malignant alteration in vitro of ST/a mouse lung fibroblasts (ST-L) have been observed. In contrast to cells which retained their fibroblastic appearance (R−ST-L cells), cells showing morphological signs of transformation (R+ST-L cells) developed strong isoimmunizing properties. Both types of cells expressed MuLV antigens which were found to be responsible for serum as well as cell-mediated immune reactions in vitro. The higher concentration of gp70 in R+ cells as compared to R− cells and possibly also the morphological differences in surface structure between the two cell types may account for the differences in immunogenicity. Preimmunization with R+ST-L cells protected ST/a mice against secondary challenge with two ascites tumors (STABAL leukemia and Ehrlich). R−ST-L cells did not have a similar protective effect. However, the two ascites tumors only showed weak or no cross-reactions in vitro with sera and lymphoid cells from ST/a mice sensitized to R+ST-L cells, and the in vitro reaction between the latter cells and sera or lymphoid cells from mice immunized against the two ascites tumors was moderate. This discrepancy between in vivo and in vitro observations is discussed.

Immunological cross-reactivities between rat spontaneous mammary carcinoma or ethylnitrosourea (ENU)-induced neurogenic tumors and various fetal and adult tissues were tested in vitro by the migration inhibition test (MIT). Wistar/Fib rats were immunized with either live cells or radiation-killed tumor cells of over 37 transplant generations. ENU-induced neurinomas of the peripheral nerve (T1, T3) lost some of their antigenicities in the later transplantation generations, and failed to react with fetal or brain tissues. On the other hand, ENU-induced oligodendroglioma (T5) retained strong antigenicities at least up to the 10th passage. In addition, T5 and syngeneic spontaneous mammary carcinoma (T9) showed similar responses to fetal extracts. Among the tissues examined, two-week fetal tissues showed the highest expression of fetal antigens detected by cross-reaction with these tumor cells. MIT with 3M KG extracts of fetal tissues demonstrated that sensitization with live tumor cells elicited stronger immunological responses than that with radiationkilled cells.

The radiosensitizing effect of misonidazole was studied in an experimental system of intracranially transplanted 203-glioma in C57BL mice. When 5 × 105 tumor cells were transplanted into the right frontal area of 4-week-old male mice, all the control mice died within 3 weeks after transplantation. The experimental mice were treated with 1, 000 rads of irradiation using 60Co, with or without misonidazole administration, given after various lengths of time after transplantation. When used, misonidazole was given intraperitoneally in a dose of 20 mg, 30 to 60 minutes prior to irradiation. Misonidazole had no remarkable effect when the mice were treated 6 days after transplantation. However, when they were treated with misonidazole 10 days after transplantation and irradiated, the mean survival time of the mice was longer (about 6.5 weeks) than that of the mice treated by irradiation alone (about 4.5 weeks). In order to evaluate the radiosensitizing effect of misonidazole in the terminal stage to contain a large number of hypoxic tumor cells, the following in vivo assay was designed. Intracranial tumors, with or without misonidazole treatment, were removed immediately after irradiation. Then, 5×105 viable tumor cells were retransplanted into other groups of mice, and their survival rates were observed. While all the mice retransplanted with tumor cells treated by irradiation alone died of tumor growth within 5 weeks, those retransplanted with tumor cells treated by irradiation and misonidazole became free of tumor and survived for the observation period of 8 weeks. These results suggest the radiosensitizing effect of misonidazole. As regards the side effects, there was no notable decrease in body weight after the administration of misonidazole. On histological examination there was no specific change ascribable to misonidazole, while there were many necrotic regions after irradiation with or without misonidazole. As a clinical trial, misonidazole was given to 21 patients with brain tumors in an oral dose of 1.0 g/m2, 4 to 6 hours prior to irradiation twice weekly. The total dose was limited to 10 g/m2. Because the series of patients was not large enough and because most of them were also given chemotherapy, it was difficult to distinguish the effect of misonidazole from that of conventional radiotherapy and chemotherapy. There was no remarkable side effects due to misonidazole except for nausea and vomiting in some patients. It is clear, however, that the limiting factor in the clinical dose of misonidazole is its various toxicities, such as peripheral neuropathy and gastrointestinal symptoms, which have occasionally been reported, and so the local application of misonidazole may be the next step.

Cross-reactivities between chemically induced rat tumors and fetal tissues were examined by the migration inhibition test. Wistar/Fib adult rats were immunized by intracutaneous injection of Freund incomplete adjuvant with or without the extracts of various fetal tissues (one-week whole fetal tissue, two-week fetus without brain and spinal cord, and two-week fetal brain). A mixture of thymic and lymph-node cells was used as migration cells. Peripheral neurinomas (T1 and T3) and oligodendroglioma (T2) were induced by ethylnitrosourea with single intraperitoneal injection in pregnant rats in the third week of gestation; 3M KCl extracts of these tumors served as antigens. The animals sensitized by two-week fetus reacted with all neurogenic tumors although in half of them (4/8) no significant differences from the reaction of the lymphoid cells sensitized by Freund incomplete adjuvant alone were demonstrated. The lymphoid cells sensitized by one-week fetus showed the weakest responses (especially in the reaction with T3 tumor) among all fetal extracts. The T1 tumor was also suggested to have brain specific antigens. When the lymphnode cells served independently as the migration cells, it was very difficult to obtain positive results which were easily obtained by a mixture of lymph-node cells and thymic cells. However, the lymph-node cells sensitized by one-week fetus reacted much more strongly than the mixture of thymic and lymph-node cells. In vivo tumor rejection studies on the embryonic tissue of immunized rats are now in progress.

The authors previously reported a new, in vitro technique for determining the invasiveness of four rat neurogenic tumor cell lines. Now this method has been modified and applied to the analysis of the invasiveness of human brain tumors. Eighty-seven tumors, including 61 gliomas, six metastatic brain tumors, 10 meningiomas, four neurinomas, one melanoma, one hemangioblastoma, two craniopharyngiomas, one chemodectoma, and one pituitary adenoma, were studied. Since gliomas were of primary interest, their invasiveness was studied more extensively. Fresh tumor specimens obtained during craniotomy were immediately minced in Dulbecco's modified Eagles's minimum essential medium containing 20% fetal calf serum to obtain fragments of 300-500 μm in size. These tumor fragments and precultured embryonic chick heart fragments were placed together on semisolid agar (0.35%) for 2 hours at 37°C. These fused tissues were then cultured in a gyratory shaker at 100 rpm for 7 days. From hematoxylin-eosin stained and immunostained serial sections, the degree of invasiveness was determined according to the “classification of invasiveness.” Although there were discrepancies between the histologic findings and the degree of invasiveness in 22.5% of high-grade astrocytomas, conventional histological diagnosis was well correlated with invasiveness in almost all low-grade astrocytomas. This in vitro technique appears to be a simple and useful means of evaluating the invasive potential of brain tumors.

IL-5 expresses various biologic effects on several types of lymphocytes, including B cells, eosinophils, and T cells. We demonstrated that the incubation of resting splenocytes from C57BL/6 mice in murine rIL-5 enhances IL-2-mediated lymphokine-activated killer (LAK) activity against various tumor cells. IL-5 alone, however, does not induce killer activity. IL-2-mediated LAK activity increases in proportion to the dose of IL-5. During the late phase of the culture period, IL-5 seems to have some effect on the induction of IL-2-mediated LAK activity. We expect that IL-5 will prove useful for adoptive immunotherapy.

This paper presents an application of parallel processing and pipeline processing to power system analysis. The system matrix is transformed to a bordered block diagonal form (BBDF) matrix for effective utilization of the processors. After LU factorization, subnetworks organize sparse matrices and the boundary network organizes a full matrix. First, a parallel processing technique is used to calculate subnetworks. Then, as pipeline processing is applied, inverse matrix of the boundary network is multiplied. The proposed method is made operational on a parallel computing system including a pipeline processor. A consideration on the transient stability analysis using the proposed method also is presented at the end of this paper.