Biomedical subjects

A Sasaki

Publications and source records attributed to A Sasaki.

At least 37 records · Page 2Linked to original sources

PubMed2003

Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells for the initiation of antigen-specific immune responses, and antigen-loaded DCs have been regarded as promising vaccines in cancer immunotherapy. We previously demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) could attain highly efficient gene transduction into human and murine DCs. The aim of the present study is to demonstrate the predominance of ex vivo genetic DC manipulation using AdRGD in improving the efficacy of DC-based immunotherapy targeting gp100, a melanoma-associated antigen (MAA). Vaccination with murine bone marrow-derived DCs transduced with AdRGD encoding gp100 (AdRGD-gp100/mBM-DCs) dramatically improved resistance to B16BL6 melanoma challenge and pulmonary metastasis as compared with immunization with conventional Ad-gp100-transduced mBM-DCs. The improvement in antimelanoma effects upon immunization with AdRGD-gp100/mBM-DCs correlated with enhanced cytotoxic activities of natural killer (NK) cells and B16BL6-specific cytotoxic T lymphocytes (CTLs). Furthermore, in vivo depletion analysis demonstrated that CD8(+) CTLs and NK cells were the predominant effector cells responsible for the anti-B16BL6 immunity induced by vaccination with AdRGD-gp100/mBM-DCs, and that helper function of CD4(+) T cells was necessary for sufficiently eliciting effector activity. These findings clearly revealed that highly efficient MAA gene transduction to DCs by AdRGD could greatly improve the efficacy of DC-based immunotherapy against melanoma.

Adenoviridae↗

PubMed2003

Current-sensing scanning near-field optical microscopy using a metal probe for nanometre-scale observation of electrochromic films.

A novel technique for scanning near-field optical microscopy capable of point-contact current-sensing was developed in order to investigate the nanometre-scale optical and electrical properties of electrochromic materials. An apertureless bent-metal probe was fabricated in order to detect optical and current signals at a local point on the electrochromic films. The near-field optical properties could be observed using the local field enhancement effect generated at the edge of the metal probe under p-polarized laser illumination. With regard to electrical properties, current signal could be detected with the metal probe connected to a high-sensitive current amplifier. Using the current-sensing scanning near-field optical microscopy, the surface topography, optical and current images of coloured WO3 thin films were observed simultaneously. Furthermore, nanometre-scale electrochromic modification of local bleaching could be performed using the current-sensing scanning near-field optical microscopy. The current-sensing scanning near-field optical microscopy has potential use in various fields of nanometre-scale optoelectronics.

Journal Article↗

PubMed2003

Successful en-bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood.

En-bloc resection is desirable for accurate histopathological assessment of tissue specimens obtained using endoscopic mucosal resection (EMR). A new EMR method using sodium hyaluronate and a small-caliber-tip transparent hood has been developed. This is a peeling-off method using a needle-knife for mucosal and submucosal incisions. Long-lasting submucosal thickening resulting from an injection of sodium hyaluronate, and good visualization of the submucosal tissue with the aid of a small-caliber-tip transparent hood, make the cutting procedures easy and safe. A large superficial gastric cancer and a large villous tumor of the sigmoid colon were endoscopically resected using this method. En-bloc endoscopic resection was successful in both patients. The gastric lesion was an well-differentiated intramucosal adenocarcinoma, completely resected in a specimen measuring 97 x 50 mm. The colonic lesion was an intramucosal well-differentiated adenocarcinoma in adenoma, completely resected in a specimen measuring 70 x 55 mm in diameter. No significant complications were noted in either patient. The new method of EMR using sodium hyaluronate and the small-caliber-tip transparent hood is a promising method for endoscopic en-bloc resection of large superficial neoplastic lesions, both in the stomach and the colon.

Adenocarcinoma↗

PubMed2003

Helicobacter pylori infection influences tumor growth of human gastric carcinomas.

BACKGROUND: Helicobacter pylori infection is considered a risk factor for gastric carcinoma. However, the effect of eradication therapy in gastric carcinoma patients is not well known. The aim of this study was to investigate the relationship between H. pylori infection and tumor growth of gastric carcinoma. METHODS: Fifty-one patients with gastric carcinoma participated in the study. Thirty-three were H. pylori-positive, 6 were H. pylori-negative, and 12 were diagnosed with gastric carcinoma after eradication of H. pylori. To investigate tumor growth of gastric carcinoma, cell proliferation and angiogenesis of the tumors were evaluated by immunohistochemical techniques using Ki-67 and CD34. RESULTS: The Ki-67 labeling index was 47.9 +/- 2.6 (mean +/- s) in the H. pylori-positive group, 38.1 +/- 3.6 in the H. pylori-eradicated group, and 22.2 +/- 5.5 in the H. pylori-negative group. It was significantly lower in the H. pylori-eradicated and H. pylori-negative groups than in the H. pylori-positive one, and a significant difference was also found between the H. pylori-positive and H. pylori-eradicated groups. The microvessel counts were 62.5 +/- 3.0, 50.2 +/- 4.0, and 66.0 +/- 9.8 in the positive, eradicated, and negative groups, respectively. A significant difference was found between the H. pylori-positive and H. pylori-eradicated groups. CONCLUSION: Our results suggest that H. pylori infection is associated with cell proliferation, and its eradication may influence tumor vascularity of gastric carcinoma. Therefore, H. pylori eradication therapy may contribute to the suppression of tumor growth.

Aged↗

PubMed2003

Association between craniofacial growth and urinary bone metabolic markers (pyridinoline, deoxypyridinoline) in growing rats.

Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are intermolecular cross-links of mature collagen and reflect the bone turnover. The purpose of this study was to elucidate the association between craniofacial growth and urinary Pyr and Dpyr levels. Lateral cephalograms and 24-hour urine were taken for 7 male rats from 5 to 20 wks old. The urinary Pyr and Dpyr were quantified by high-performance liquid chromatography. The neurocranium and upper viscerocranium exhibited significant increases in size, with the maximum rate at around 6 wks old. The mandible presented more substantial growth, with the maximum change at 8 wks old. The urinary Pyr and Dpyr levels gradually increased and reached the maximum at 8 wks old. No prominent association was found between neurocranial growth and urinary levels of pyridinium cross-links, whereas Pyr and Dpyr levels exhibited similar time-dependent metabolic changes to mandibular growth. In conclusion, it is shown that urinary pyridinium cross-links may be useful for the prediction of mandibular growth.

Age Factors↗

PubMed2003

[Penetrating cardiac and pulmonary injury by a nail-gun: report of a case].

A 64-year-old man underwent emergency operation for self-inflicted penetrating cardiac and pulmonary injury by a nail-gun. Chest films on admission showed 5 nails penetrating the thorax and one of these nails had reached into pericardium. Emergency surgery was performed by median sternotomy and the 5 nails in the chest wall were totally removed and the wound of right ventricle and lung were closed with direct mattress sutures without cardio-pulmonary bypass. Post operative course was uneventful and he was transferred to the psychiatric ward for the treatment of depression at post operative 7 days.

Cardiac Surgical Procedures↗

PubMed2003

Acquisition of a gastric or duodenal phenotype on heterotropic transplantation of esophagus and bladder tissues in F344 rats.

Cell differentiation is very important but not well understood. In the present study the ability of various tissues to newly-differentiate when transplanted into the fundus or the duodenum in rats was tested. Pieces of esophagus, bladder, diaphragm and trachea from 8-week-old male F344 rats were transplanted into the gastric fundus or duodenum of females and examined after 3 or 6 months. While the diaphragm was not recognizable as a muscle layer in either the stomach or the duodenum, the esophagus and trachea persisted, the latter with the presence of cartilage. Esophagus grafts transplanted into the glandular stomach and duodenum, newly-differentiated into gastric and duodenal mucosa, respectively. Goblet cells with alcian-blue positive mucin appeared in bladder tissue implanted into the duodenum. Six months after the operation, their numbers had increased and cytoplasm alkaline phosphatase (ALP) positivity was noted. Gastrointestinal and also bladder stem cells may thus have multipotential ability for differentiation and may be able to newly-differentiate when transplanted into different environments in the gastrointestinal tract.

Animals↗

PubMed2002

Ion acceleration in a solitary wave by an intense picosecond laser pulse.

Acceleration of ions in a solitary wave produced by shock-wave decay in a plasma slab irradiated by an intense picosecond laser pulse is studied via particle-in-cell simulation. Instead of exponential distribution as in known mechanisms of ion acceleration from the target surface, these ions accelerated forwardly form a bunch with relatively low energy spread. The bunch is shown to be a solitary wave moving over expanding plasma; its velocity can exceed the maximal velocity of ions accelerated forward from the rear side of the target.

Journal Article↗

PubMed2002

Human GLUT5 immunolabeling is useful for evaluating microglial status in neuropathological study using paraffin sections.

In neuropathological studies it is important to detect both resting and reactive microglia in paraffin sections. We examined the usefulness of human (h) GLUT5, a glucose transporter, as a microglial marker. We produced an hGLUT5 antibody against its C-terminal sequence and stained human brain tissue sections. The hGLUT5 antibody consistently stained microglia in cryostat sections. In paraffin sections fixed with formalin, paraformaldehyde or ethanol, both resting and reactive microglia were stained; the latter were stained more intensely than the former. The hGLUT5 and glial fibrillary acidic protein labeling did not overlap each other in double immunofluorescence analyses. Oligodendrocytes, perivascular cells, choroid plexus epithelium and ependymal cell were negative for hGLUT5. Even after 1-month fixation in formalin, the hGLUT5 antibody stained microglia well. Microwave pretreatment enhanced the immunoreactivity of hGLUT5. As compared with other microglial markers, KP-1, KiM1p, CR3.43 and RCA-1, the hGLUT5 antibody could be considered good morphological marker. hGLUT5 immunolabeling clearly showed the detailed microglial processes, whereas immunolabeling with Ki-M1P and KP-1 showed cytoplasmic granules, and it was difficult to trace the microglial processes. The hGLUT5 antibody stained both resting and reactive microglia, whereas CR3.43 stained only reactive microglia, and RCA-1 labeled microvessels more intensely than microglia. Thus, hGLUT5 is a marker that is suitable for routine histopathological staining procedures.

Adult↗

PubMed2002

Clone mixtures and a pacemaker: new facets of Red-Queen theory and ecology.

Host-parasite antagonistic interaction has been proposed as a potential agent to promote genetic polymorphism and to favour sex against asex, despite its twofold cost in reproduction. However, the host-parasite gene-for-gene dynamics often produce unstable cycles that tend to destroy genetic diversity. Here, we examine such diversity destroying coevolutionary dynamics of host and parasite, which is coupled through local or global migration, or both, between demes in a metapopulation structure. We show that, with global migration in the island model, peculiar out-of-phase islands spontaneously arise in the cluster of islands converging to a global synchrony. Such asynchrony induced by the 'pacemaker islands' serves to restore genetic variation. With increasing fraction of local migration, spots of asynchrony are converted into loci or foci of spiral and target patterns, whose rotating arms then cover the majority of demes. A multi-locus analogue of the model reproduces the same tendency toward asynchrony, and the condition arises for an advantage of asexual clones over their sexual counterpart when enough genetic diversity is maintained through metapopulation storage-migration serves as a cheap alternative to sex.

Animals↗

PubMed2002

Radiation damping effects on the interaction of ultraintense laser pulses with an overdense plasma.

A strong effect of radiation damping on the interaction of an ultraintense laser pulse with an overdense plasma slab is found and studied via a relativistic particle-in-cell simulation including ionization. Hot electrons generated by the irradiation of a laser pulse with a radiance of I lambda(2)>10(22) W microm(2)/cm(2) and duration of 20 fs can convert more than 35% of the laser energy to radiation. This incoherent x-ray emission lasts for only the pulse duration and can be intense. The radiation efficiency is shown to increase nonlinearly with laser intensity. Similar to cyclotron radiation, the radiation damping may restrain the maximal energy of relativistic electrons in ultraintense-laser-produced plasmas.

Journal Article↗

PubMed2002

Green revolution: a mutant gibberellin-synthesis gene in rice.

The chronic food shortage that was feared after the rapid expansion of the world population in the 1960s was averted largely by the development of a high-yielding semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'. The short stature of IR8 is due to a mutation in the plant's sd1 gene, and here we identify this gene as encoding an oxidase enzyme involved in the biosynthesis of gibberellin, a plant growth hormone. Gibberellin is also implicated in green-revolution varieties of wheat, but the reduced height of those crops is conferred by defects in the hormone's signalling pathway.

Crops, Agricultural↗

PubMed2002

Viscoelastic properties and residual strain in a tensile creep test on bovine temporomandibular articular discs.

This study was designed to evaluate the creep characteristics and residual strain of bovine temporomandibular joint (TMJ) discs in tension. Twenty discs were divided into three specimens each: central, lateral and medial regions. Tension of 1.0 MPa was applied and sustained for 20 min to the specimens from 10 right-side discs, and tension of 1.5 MPa to specimens from 10 left-side discs. After the period of tension for creep, the specimens were removed from the tension devices and restoration observed for 20 min. Time-dependent creep curves showed a marked change in strain during the initial 5s. The essential time delay in strain ceased after 2 min, and strain reached an almost steady level after 3 min. At a tensile stress of 1.5 MPa, a strain of 14.5% on average was produced after 20 min creep in the central specimens; peripheral specimens showed strains of 12.4% on average. There were significant differences in strain between the central and peripheral specimens. The residual strain after 20 min restoration was 0.93% on average and there were no significant regional differences. This creep feature could be well represented by a generalized linear viscoelastic model. It was concluded that the regional differences in viscoelasticity might be caused by the complicated articulating functions of the TMJ, and that the residual strain caused by sustained stress could be an important factor in disc deformation.

Animals↗

PubMed2002

A case of Kimura's disease of the hard palate.

A 33-year-old man presented with Kimura's disease of the hard palate. Serological examination showed no elevation in the number of eosinophils or in IgE level, but histological examination revealed well-developed lymph follicles with increased numbers of eosinophils. In addition, immunohistochemical examination revealed that the IgE concentrations were shown in the lymphoid follicles with germinal centers, a finding typical of Kimura's disease. The patient underwent surgical resection followed by treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Throughout the 2-year follow-up period, the patient's condition has remained satisfactory.

Adult↗

PubMed2002

Role of anti-parietal cell antibody in Helicobacter pylori-associated atrophic gastritis: evaluation in a country of high prevalence of atrophic gastritis.

BACKGROUND: Helicobacter pylori plays an important part in the progression of atrophic gastritis; however, markers for predicting the progression of atrophic gastritis remain unidentified. We investigated the relation between the degree of atrophic gastritis and the amount of anti-parietal cell antibodies (APCAs) present. METHODS: In 219 Japanese patients, APCA was investigated by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The grade of corpus atrophy was estimated by histology and serum pepsinogen levels. Serum levels of pepsinogen were evaluated by radioimmunoassay. RESULTS: Helicobacter pylori infection did not affect the APCA levels determined by ELISA. Long-term administration of proton-pump inhibitors and H. pylori eradication did not influence the levels of APCAs. However, in H. pylori-positive patients, the levels of APCA determined by ELISA were statistically higher in patients with severe atrophy than in those with mild atrophy as determined histologically (0.67+/-0.48 versus 0.45+/-0.40; A492, mean+/-s, P=0.01) and serologically by pepsinogen levels (0.66+/-0.51 versus 0.44+/-0.40. P=0.002). The levels of pepsinogen I/II ratio were correlated with APCA levels only in the H. pylori-positive group. Western blotting showed that major antigen was identical with the beta-subunit of H+,K+-ATPase. CONCLUSION: APCA plays an important part in the progression of corpus atrophy after H. pylori infection.

Adolescent↗

PubMed2001

Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line.

Connective tissue growth factor (CTGF) is known to be a potent angiogenic factor. Here, we present the evidence that the hypoxic induction of angiogenesis by human breast cancer cells (MDA-231) can be ascribed at least in part to CTGF. Our results indicate that (i) CTGF is abundantly present in MDA-231 cells in vitro and in vivo, (ii) its secretion is up-regulated by hypoxia, and (iii) its gene expression is enhanced in MDA-231 cells cultured under hypoxic conditions. These data suggest CTGF may stimulate angiogenesis by paracrine mechanisms, thereby contributing to the invasion of breast cancer cells. This is the first evidence that human cancer cells differentially express CTGF protein and mRNA under the control of hypoxic conditions.

Angiogenesis Inducing Agents↗

PubMed2001

The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas.

Reduction of E-cadherin strongly relates to invasiveness and metastasis in vitro. To clarify CpG methylation around the promoter region of the E-cadherin gene in oral squamous cell carcinoma (SCC), we examined the DNA samples of various human SCC cell lines and primary oral SCC tissues by methylation-specific polymerase chain reaction (MSP). CpG methylation of the E-cadherin gene markedly correlated to the reduction of E-cadherin expression in human oral SCC cell lines. In primary oral SCC tissues, only 1 of 5 preserved E-cadherin-expressing tissues was methylated, whereas methylation was found in 17 (94.4%) of 18 E-cadherin-reduced tissues. Our results suggest that reduction of E-cadherin expression is associated with CpG methylation of the E-cadherin gene promoter. We recently established two cell lines with high and low metastatic potential, UM1 and UM2, from SCC primary tongue tissue of a patient. E-cadherin expression of high-metastatic UM1 was clearly lower than that of low-metastatic UM2, and MSP results showed CpG methylation in the UM1 but not the UM2 cell line. To investigate whether demethylation of CpG methylation of the E-cadherin gene could restore expression and function of E-cadherin, we treated UM1 with the demethylating agent 5-azacytidine (5-aza) and found that E-cadherin expression was indeed restored by demethylation. Moreover, in the demethylated UM1, invasion of the collagen gel was clearly suppressed compared with the untreated UM1. These results suggested that inactivation of E-cadherin expression resulted from CpG methylation of the gene promoter; a correlation between CpG methylation of the E-cadherin gene promoter and invasive potential was also suggested.

Antimetabolites, Antineoplastic↗

PubMed2001

Spred is a Sprouty-related suppressor of Ras signalling.

Cellular proliferation, and differentiation of cells in response to extracellular signals, are controlled by the signal transduction pathway of Ras, Raf and MAP (mitogen-activated protein) kinase. The mechanisms that regulate this pathway are not well known. Here we describe two structurally similar tyrosine kinase substrates, Spred-1 and Spred-2. These two proteins contain a cysteine-rich domain related to Sprouty (the SPR domain) at the carboxy terminus. In Drosophila, Sprouty inhibits the signalling by receptors of fibroblast growth factor (FGF) and epidermal growth factor (EGF) by suppressing the MAP kinase pathway. Like Sprouty, Spred inhibited growth-factor-mediated activation of MAP kinase. The Ras-MAP kinase pathway is essential in the differentiation of neuronal cells and myocytes. Expression of a dominant negative form of Spred and Spred-antibody microinjection revealed that endogenous Spred regulates differentiation in these types of cells. Spred constitutively associated with Ras but did not prevent activation of Ras or membrane translocation of Raf. Instead, Spred inhibited the activation of MAP kinase by suppressing phosphorylation and activation of Raf. Spred may represent a class of proteins that modulate Ras-Raf interaction and MAP kinase signalling.

Adaptor Proteins, Signal Transducing↗