PubMed Health⌕ Search

Biomedical subjects

Keiji Shimizu

Publications and source records attributed to Keiji Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

[Comparison of noise equivalent count rate and image quality for two-dimensional and three-dimensional PET scans].

The aim of this study was to investigate the correlation between noise equivalent count (NEC) rates and the signal-to-noise ratio (S/N) in reconstructed images. The NEC rates were determined using uniform 20 cm and 70 cm tall, 20 cm diameter cylinders filled with 11C. The phantoms were scanned in both two-dimensional and three-dimensional modes. The reconstructed image noise was evaluated using FBP and OSEM algorithms (4 iterations and 8 subsets). The images were filtered to a final image resolution of 6.5 mm. From the reconstructed image sets, averages and standard deviations of images were generated, from which the average image S/N (=average/standard deviation) was calculated within an 18 cm central ROI. The S/N of a central slice and an end slice was compared with the NEC. The NEC was found to have a linear relationship to the image S/N of all slices, depending on differences in noise properties specific to the reconstruction algorithm. In two-dimensional mode, although the image S/N of the central slice and the edge slice showed a linear relationship with the NEC, in three-dimensional mode, the S/N of the central slice did not show a relationship with the NEC. The linear relationship was also found in both two- and three-dimensional acquisition modes, as well as for the different activity distributions. These results indicate that the NEC is not only a measure for comparing the count rate performance of imaging systems. However, an absolute evaluation is impossible to depend on reconstruction algorithm, slice number, and phantom type.

Algorithms↗
PubMed2006

Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.

Recent studies have suggested that dendritic cell (DC)-based immunotherapy is one promising approach for the treatment of cancer. We previously studied the clinical toxicity, feasibility, and efficacy of cancer vaccine therapy with peptide-pulsed DCs. In that study, we used granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood monocytes as a cell source of DCs. However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. These T helper (Th)-1-type cytokines are thought to promote antitumor immune response. In this study, we assessed the functional abilities of DCs generated from G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers. Peripheral blood mononuclear cells were obtained from leukapheresis products collected before and after systemic administration of G-CSF (subcutaneous administration of high-dose [5-10 microg/kg] human recombinant G-CSF for five consecutive days). In vitro cytokine production profiles after stimulation with lipopolysaccharide (LPS) were compared between monocytes with and without G-CSF mobilization. DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptide-specific T cell responses. Administration of G-CSF was found to efficiently mobilize peripheral blood monocytes. Although G-CSF-mobilized monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored the same level of IL-12 production as that seen in DCs generated from C/Mo. T cell induction assay using recall antigen peptide and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated from C/Mo. Our results suggest that G-CSF mobilization can be used to collect monocytes as a cell source for the generation of DCs for cancer immunotherapy. DCs generated in this fashion were pulsed with HLA-A24-restricted CEA epitope peptide and administered to patients safely; immunological responses were induced in some patients.

Adult↗
PubMed2006

Clinico-pathological significance of RCAS1 expression in gliomas: a potential mechanism of tumor immune escape.

RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape.

Adolescent↗
PubMed2006

Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells.

Motoneurons and oligodendrocytes in the embryonic spinal cord are produced from a restricted domain of the ventral ventricular zone, termed the pMN domain. The pMN domain is the site of expression of two basic helix-loop-helix transcription factors, Olig1 and Olig2, which are essential for motoneuron and oligodendrocyte development. Previous lineage-tracing experiments using Olig1-Cre and Olig2-GFP mice suggested that motoneurons and oligodendrocytes, but not astrocytes, are produced from the pMN domain. However, important questions remain, including the fate of neuroepithelial cells in the pMN domain, and specifically whether motoneurons and oligodendrocytes are the only types of cells produced in the pMN domain. We performed lineage-tracing experiments using a tamoxifen-inducible Cre-recombinase inserted into the Olig2 locus. We demonstrated that motoneurons and oligodendrocyte progenitors are derived from the Olig2+ progenitors in the pMN domain, and also found that a subset of astrocytes at the ventral surface of the spinal cord and ependymal cells at the ventricular surface are also produced from the pMN domain. These findings demonstrate that motoneurons and oligodendrocytes are not the only cell types originating from this domain.

Animals↗
PubMed2006

[Accuracy of attenuation coefficient obtained by 137Cs single-transmission scanning in PET: comparison with conventional germanium line source].

UNLABELLED: Transmission scanning can be successfully performed with a Cs-137 single-photon-emitting point source for three-dimensional PET imaging. This method was effective for postinjection transmission scanning because of differences in physical energy. However, scatter contamination in the transmission data lowers measured attenuation coefficients. The purpose of this study was to investigate the accuracy of the influence of object scattering by measuring the attenuation coefficients on the transmission images. We also compared the results with the conventional germanium line source method. METHODS: Two different types of PET scanner, the SET-3000 G/X (Shimadzu Corp.) and ECAT EXACT HR(+) (Siemens/CTI) , were used. For the transmission scanning, the SET-3000 G/X and ECAT HR(+) were the Cs-137 point source and Ge-68/Ga-68 line source, respectively. With the SET-3000 G/X, we performed transmission measurement at two energy gate settings, the standard 600-800 keV as well as 500-800 keV. The energy gate setting of the ECAT HR(+) was 350-650 keV. The effects of scattering in a uniform phantom with different cross-sectional areas ranging from 201 cm(2) to 314 cm(2) to 628 cm(2) (apposition of the two 20 cm diameter phantoms) and 943 cm(2) (stacking of the three 20 cm diameter phantoms) were acquired without emission activity. First, we evaluated the attenuation coefficients of the two different types of transmission scanning using region of interest (ROI) analysis. In addition, we evaluated the attenuation coefficients with and without segmentation for Cs-137 transmission images using the same analysis. The segmentation method was a histogram-based soft-tissue segmentation process that can also be applied to reconstructed transmission images. RESULTS: In the Cs-137 experiment, the maximum underestimation was 3% without segmentation, which was reduced to less than 1% with segmentation at the center of the largest phantom. In the Ge-68/Ga-68 experiment, the difference in mean attenuation coefficients was stable with all phantoms. CONCLUSION: We evaluated the accuracy of attenuation coefficients of Cs-137 single-transmission scans. The results for Cs-137 suggest that scattered photons depend on object size. Although Cs-137 single-transmission scans contained scattered photons, attenuation coefficient error could be reduced using by the segmentation method.

Cesium Radioisotopes↗
PubMed2006

[Optimization of basic adjustable data-acquisition parameters for continuous three-dimensional whole-body FDG-PET].

UNLABELLED: The SET-3000 G/X (Shimadzu Corp., Kyoto, Japan) has a large aperture and functions as a three-dimensional (3D) dedicated PET scanner. However, the large number of line of responses in the SET-3000 G/X scanner creates a large volume of sinogram data and prolongs reconstruction time in iterative reconstruction. The purpose of this study was to optimize basic acquisition parameters (maximum ring difference and span) for sensitivity and spatial resolution for 3D whole-body (18)F-FDG PET. METHODS: Detector rings and image planes numbered 50 and 99, respectively. In sensitivity measurement, the maximum ring difference (MRD) was changed from 1 to 49. In the measurement of spatial resolution, the span was changed from 3 to 21. For sensitivity and spatial resolution measurements, the standard protocols defined by the Japan Radioisotope Association (JRIA) 1994 and the National Electrical Manufacturers Association (NEMA) NU 2-2001 were used. We also evaluated the corresponding image noise by placing identical ROI on the reconstructed images. RESULTS: The total sensitivity of MRD=49 was 85.7 cps/Bq/ml in a uniform phantom (15 cm diameter, 30 cm tall cylinder) filled with (18)F. This was approximately two times higher than MRD=13. The image noise in the center of the axial FOV decreased with increasing MRD. Spatial resolution was slightly decreased as MRD increased, but axial resolution deteriorated with a span of more than 11. CONCLUSION: Optimum basic data-acquisition parameters for whole-body (18)F-FDG PET were MRD 49 to obtain maximum sensitivity and span 9 to avoid decreasing spatial resolution. Additionally, it was concluded that the basic data-acquisition parameters should be carefully selected for 3D whole-body (18)F-FDG PET in order to maximize the efficiency of PET measurement.

Electronic Data Processing↗
PubMed2006

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Antigen-Presenting Cells↗
PubMed2006

Induction of cytotoxic T lymphocytes against human cancer cell lines using dendritic cell-tumor cell hybrids generated by a newly developed electrofusion technique.

Recently, dendritic cells (DCs) and DC-tumor cell hybrids (DC-tumor hybrids) have been used for cancer vaccine therapy in a clinical trial. DC-tumor hybrids combine the potent antigen-presenting capacity of DCs with the ability to present all tumor antigens expressed on tumor cells to T cells. We used DC-tumor hybrids as stimulator cells to induce tumor-specific cytotoxic T lymphocytes (CTLs) in vitro. DC-tumor hybrids were generated from human monocyte-derived DCs and human cancer-cell lines (GT3TKB, lung cancer; GCIY, gastric cancer) by our newly developed electrofusion technique, established and refined with the use of mouse cells. To evaluate the capacity of DC-tumor hybrids generated by our method to induce tumor antigen-specific CTLs, we performed a cytotoxic assay and an interferon-gamma release assay using CD8-dominant effector lymphocytes induced by them. DC-tumor hybrids more effectively induced tumor-specific primary T-cell response than did stimulation with DCs co-cultured with irradiated tumor cells overnight, irradiated tumor cells alone, or a mixture of DCs and irradiated tumor cells. DC-tumor hybrids were generated at a high fusion rate by our electrofusion technique. When CTLs were induced by DC-tumor hybrids in vitro, the high fusion rate did not contribute to the induction of CTLs with increased tumor-specific cytotoxicity. The addition of interleukin-12 to the culture medium did not augment the cytotoxicity of CTLs. Overall, our results suggest that DC-tumor hybrids effectively induce human tumor-specific CTLs and may thus be applicable for clinical trials of adoptive immunotherapy.

Adenocarcinoma↗
PubMed2005

Expression of MAGE-D4, a novel MAGE family antigen, is correlated with tumor-cell proliferation of non-small cell lung cancer.

PURPOSE: MAGE-D4, originally termed MAGE-E1, is a novel MAGE family gene that is expressed at high levels in malignant tumors as compared to normal tissue. The present study was conducted to assess the clinical significance of MAGE-D4 expression in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of MAGE-D4 protein was estimated by immunohistochemistry and MAGE-D4 mRNA expression was investigated using quantitative reverse transcription-PCR (RT-PCR). RESULTS: We assessed MAGE-D4 expression in NSCLC tissues and was found to be up-regulated in tumor tissues compared with normal lung tissues (mean MAGE-D4/GAPDH values, 0.035 for tumor tissues and 0.009 for normal lung tissues; p=0.002). However, there was no significant difference in MAGE-D4 expression among different pathological stages. The proliferative activity of tumor cells was significantly higher in high MAGE-D4 tumors (mean proliferative indices, 58.3 for high MAGE-D4 tumor levels and 34.0 for low MAGE-D4 tumor levels; p<0.001). In addition, a high MAGE-D4 expression was more frequently seen in squamous cell carcinoma than in adenocarcinoma (p=0.008), and less frequently in well-differentiated tumors than in moderately to poorly differentiated tumors (p=0.036). There was no difference in the postoperative survival between low and high MAGE-D4 patients (5-year survival rates, 65% and 69%, respectively; p=0.742). CONCLUSIONS: MAGE-D4 plays some roles in tumor cells proliferation in NSCLC, but MAGE-D4 expression status did not provided a prognostic significance.

Animals↗
PubMed2005

Titration of serum p53 antibodies in patients with gastric cancer: a single-institute study of 40 patients.

BACKGROUND: Alterations of the p53 tumor suppressor gene are the most commonly observed genetic abnormalities in many different types of human malignancies. The accumulation of mutant p53 often leads to the production of p53 antibody (p53-Ab) in the sera of patients with various cancers. To evaluate the clinical implications of serum p53-Abs in patients with gastric cancer, we compared p53-Abs with conventional tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. METHODS: Serum samples were obtained preoperatively from 40 patients with histologically confirmed gastric adenocarcinoma, including 28 (70%) patients in stage Ia. The serum p53-Abs were assessed by enzyme-linked immunosorbent assay, using a new version of a highly specific, quantitative p53-Abs Kit (MESACUP Kit II). RESULTS: p53-Abs were detected in 6 (15%) of 40 patients with gastric cancer, including 3 patients with early gastric cancer. Seven (17.5%) of the 40 patients were positive for CEA in serum. However, none of 7 patients with high CEA levels were positive for p53-Abs. No significant correlation of p53-Abs with patient age, sex, pathological parameters, tumor markers such as CEA and CA19-9, or poor survival (P = 0.116) was observed. CONCLUSION: Although we employed the latest version of the p53-Abs Kit, the sensitivity of serum p53-Ab in gastric cancer patients was relatively low. No correlation was found between the presence of p53-Ab and the staging of cancer or survival. However, serum p53-Ab was detectable in patients with gastric cancer even in the early stages of disease. In addition, it may be independent of CEA and CA19-9.

Adenocarcinoma↗
PubMed2005

Tumor-dendritic cell fusion as a basis for cancer immunotherapy.

OBJECTIVE: To establish the basis for use of allogeneic dendritic-tumor fusion cells. STUDY DESIGN: Fusion cells were created by electrofusion. We used 2 allogeneic murine tumor lines (D5 and 4T1) that were virally transduced to express the antigen (beta-galactosidase) as a surrogate tumor marker. RESULTS: Cross-immunization was achieved with irradiated allogenic tumor cells. Successful electrofusion of dendritic cells and tumor cells was confirmed by using fluorescence-activated cell sorting and cytospin. Significant responses were shown in immunized mice against tumor challenge and established 3-day pulmonary metastasis with fusion cells. CONCLUSIONS: Allogeneic tumor sharing a common tumor antigen can immunize against syngeneic tumor challenge. Fusion cells showed successful immunization against tumor challenge and showed regression of 3-day established pulmonary metastasis. SIGNIFICANCE: These preclinical studies provide evidence that an allogenic tumor-dendritic cell fusion vaccine is a valid approach for head and neck cancer immunotherapy.

Animals↗
PubMed2005

A rapidly enlarging nocardial brain abscess mimicking malignant glioma.

Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, (201)TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.

Brain Abscess↗
PubMed2004

Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma.

We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90% of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation.

Animals↗
PubMed2004

Improved preservation of X-gal reaction product for electron microscopy using hydroxypropyl methacrylate.

In lineage tracing analysis, the beta-galactosidase (beta-gal) gene is a commonly used as a reporter gene because it is relatively stable and highly sensitive in histochemical detection using 5-bromo-4-chloro-3-indolyl-beta-d-galactoside (X-gal). Clear determination of the types and characteristics of labeled cells requires transmission electron microscopic (TEM) examination of their morphology. X-gal staining, which involves the precipitate formed by the reaction between beta-gal and X-gal, is usually recognized as a light blue or green reaction product on light microscopic (LM) examination. However, the standard protocol for TEM preparation weakens the intensity of or results in the loss of X-gal reaction product at the step of substitution of ethanol with Epon using propylene oxide. To solve this problem, we show that hydroxypropyl methacrylate achieves good preservation of X-gal reaction products. The protocol presented here appears to be useful for lineage determination by TEM of all types of X-gal-stained tissues.

Animals↗
PubMed2004

Hemorrhagic cerebral metastases from thyroid cancer on T2*-weighted gradient echo MRI.

We report a case of multiple hemorrhagic cerebral metastases from papillary thyroid cancer, with reference to T(2)*-weighted gradient echo (GRE) magnetic resonance imaging (MRI). Small metastatic nodules were recognized as round nodules with signal loss on T(2)*-weighted GRE MRI, and were more pronounced compared with other sequences. Lesions were later confirmed as hemorrhagic on T(1)- and T(2)-weighted MRI. T(2)*-weighted GRE MRI was a sensitive tool for early detection of metastases displaying hemorrhagic changes.

Adenocarcinoma, Papillary↗
PubMed2004

Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas.

We conducted a clinical study of cancer vaccine therapy with dendritic cells (DCs) and HLA-A24-restricted carcinoembryonic antigen (CEA)-derived peptide to assess the feasibility and efficacy of such therapy. Eighteen patients with CEA-expressing metastatic gastrointestinal or lung adenocarcinomas who were positive for human leukocyte antigen (HLA)-A24 were enrolled. DCs were generated from the patients' autologous monocyte-enriched fractions of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. The generated DCs were pulsed with CEA-derived, HLA-A24-restricted 9-mer peptide (CEA652) and injected into the patients intradermally and subcutaneously every 2 weeks. Toxicity and clinical and immunological responses were closely monitored in each patient. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. Although no definite tumor shrinkage occurred in any patient, long-term stable disease or marked decreases in the serum CEA level were observed in some patients after therapy. Most of the patients in whom treatment was clinically effective showed a positive skin response to CEA652-pulsed DCs (delayed-type hypersensitivity skin test) and a positive in vitro CTL response to CEA652 peptide after therapy. We conclude that active specific immunotherapy using DCs pulsed with CEA652 is a safe and feasible treatment that is clinically effective in some patients with metastatic gastrointestinal or lung adenocarcinomas. Our results will hopefully encourage further refinement and development of DC-based immunotherapy with HLA-A24-restricted CEA-derived peptide for refractory solid cancers that express CEA.

Adenocarcinoma↗
PubMed2004

[Immunotherapeutic reactivity of dendritic cells loaded with a variety of antigen preparations].

The findings summarized here provide a direct comparison of the immunogenicity of various DC loading strategies included pulsing with protein, peptide, tumor cell lysate, irradiated tumor cells and electrofusion of DCs and tumor cells. For the treatment of 3-day established pulmonary metastases, electrofusion of DCs and tumor cells generated a therapeutic vaccine far superior to other methods of DC loading. Consistent with their therapeutic activity, fusion hybrids stimulated the release of the largest amount of interferon-gamma from immune T cells. However, IL-10 secretion did not correlate with in vivo therapeutic reactivity. In conclusion, DC-tumor fusion hybrids were the most effective vaccine to eradicate existing tumors. These data support the use of DC-tumor electrofusion cells for the treatment of human cancer.

Animals↗