Search PubMed⌕ Search

Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 19 recordsLinked to original sources
PubMed2004

Genetic diversity and phylogeny of Japanese sake-brewing rice as revealed by AFLP and nuclear and chloroplast SSR markers.

Japanese rice ( Oryza sativa L.) cultivars that are strictly used for the brewing of sake (Japanese rice wine) represent a unique and traditional group. These cultivars are characterized by common traits such as large grain size with low protein content and a large, central white-core structure. To understand the genetic diversity and phylogenetic characteristics of sake-brewing rice, we performed amplified fragment length polymorphism and simple sequence repeat analyses, using 95 cultivars of local and modern sake-brewing rice together with 76 cultivars of local and modern cooking rice. Our analysis of both nuclear and chloroplast genome polymorphisms showed that the genetic diversity in sake-brewing rice cultivars was much smaller than the diversity found in cooking rice cultivars. Interestingly, the genetic diversity within the modern sake-brewing cultivars was about twofold higher than the diversity within the local sake-brewing cultivars, which was in contrast to the cooking cultivars. This is most likely due to introgression of the modern cooking cultivars into the modern sake-brewing cultivars through breeding practices. Cluster analysis and chloroplast haplotype analysis suggested that the local sake-brewing cultivars originated monophyletically in the western regions of Japan. Analysis of variance tests showed that several markers were significantly associated with sake-brewing traits, particularly with the large white-core structure.

Analysis of Variance↗
PubMed2004

Transient induction of TGF-alpha disrupts lung morphogenesis, causing pulmonary disease in adulthood.

Clinical studies have associated increased transforming growth factor (TGF)-alpha and EGF receptor with lung remodeling in diseases including bronchopulmonary dysplasia (BPD). BPD is characterized by disrupted alveolar and vascular morphogenesis, inflammation, and remodeling. To determine whether transient increases in TGF-alpha are sufficient to disrupt postnatal lung morphogenesis, we utilized neonatal transgenic mice conditionally expressing TGF-alpha. Expression of TGF-alpha from postnatal days 3 to 5 disrupted postnatal alveologenesis, causing permanent enlargement of distal air spaces in neonatal and adult mice. Lung volume-to-body weight ratios and lung compliance were increased in adult TGF-alpha transgenic mice, whereas tissue and airway elastance were reduced. Elastin fibers in the alveolar septae were fragmented and disorganized. Pulmonary vascular morphogenesis was abnormal in TGF-alpha mice, with attenuated and occasionally tortuous arterial branching. The ratios of right ventricle weight to left ventricle plus septal weight were increased in TGF-alpha mice, indicating pulmonary hypertension. Electron microscopy showed gaps in the capillary endothelium and extravasation of erythrocytes into the alveolar space of TGF-alpha mice. Hemorrhage and inflammatory cells were seen in distal air spaces at 1 mo of age. In adult TGF-alpha mice, alveolar remodeling, nodules, proteinaceous deposits, and inflammatory cells were seen. Immunostaining for pro-surfactant protein C showed that type II cells were abundant in the nodules, as well as neutrophils and macrophages. Trichrome staining showed that pulmonary fibrosis was minimal, apart from areas of nodular remodeling in adult TGF-alpha mice. Transient induction of TGF-alpha during early alveologenesis permanently disrupted lung structure and function and caused chronic lung disease.

Animals↗
PubMed2004

Evidence for recombination among isolates of Tobacco leaf curl Japan virus and Honeysuckle yellow vein mosaic virus.

Complete nucleotide sequences of Tobacco leaf curl Japan virus (TbLCJV) isolates from infected tomato ( Lycopersicon esculentum) plants in Nara (-[Jp2], 2764 nt; -[Jp3], 2761 nt), Kochi (-[Koc], 2760 nt) and Yamaguchi (-[Yam], 2758 nt) Prefectures, of Japan were determined. These sequences were compared with each other and the sequences of further begomoviruses from Japan. TbLCJV, TbLCJV-[Jp2], TbLCJV-[Jp3], TbLCJV-[Koc], TbLCJV-[Yam], Honeysuckle yellow vein mosaic virus (HYVMV), Eupatorium yellow vein virus (EpYVV), EpYVV-[MNS2], EpYVV-[SOJ3], EpYVV-[Yam] and EpYVV-[Tob] are monophyletic. The intergenic region (IR) of TbLCJV has highest nucleotide sequence identity with that of HYVMV (93%) whereas the rest of the genomic DNA had higher identity with that of TbLCJV-[Jp2] or -[Jp3] (91 approximately 100%) than with that of HYVMV. In conclusion, TbLCJV has a chimeric genome which may have arisen by recombination between TbLCV-[Jp2] or -[Jp3]-like and HYVMV-like ancestors. Similarly, TbLCJV-[Yam] DNA has a hybrid genome, with a major parent HYVMV and minor parent TbLCJV-[Koc].

DNA, Intergenic↗
PubMed2004

Long-term follow-up study of gastric adenoma/dysplasia.

BACKGROUND AND STUDY AIMS: The natural course of gastric adenoma/dysplasia, regarded as a precancerous lesion, is still uncertain. PATIENTS AND METHODS: From 1976 to 2000, 48 lesions in 43 patients (37 men, six women; mean age 59 years) were diagnosed as having gastric adenoma/dysplasia based on their first biopsies. These lesions were followed for a median of 4.7 years (mean 6 years, range 3-18 years) to evaluate the risk of progression to invasive carcinoma. Retrospectively, histological diagnoses of the biopsy and resected specimens were reclassified according to the Vienna classification of gastrointestinal epithelial neoplasia, and macroscopic changes were evaluated. RESULTS: The diagnosis at first biopsy of the 48 lesions was low-grade adenoma/dysplasia (LGD; category 3) in 38 cases and high-grade adenoma/dysplasia (HGD; category 4) in 10 cases. Ninety-seven percent of the LGD (category 3) lesions (37 of 38) showed no histological changes during the follow-up period; the remaining lesion progressed to noninvasive carcinoma (category 4). Macroscopically, 84 % (32 of 38) of the LGD lesions (category 3) showed no remarkable changes in size, while 11 % (four of 38) shrank and 5 % (two of 38) grew larger. Nine of the 10 HGD lesions (category 4) remained histologically unchanged, while the other progressed to intramucosal carcinoma (category 5). Macroscopically, four of the 10 HGD lesions (category 4) (40 %) showed no remarkable changes in size, while the remaining six (60 %) grew larger. CONCLUSIONS: LGD lesions (category 3) have a quite low risk of progressing to HGD or noninvasive carcinoma (category 4), and were never observed to progress to invasive carcinoma (category 5). HGD lesions (category 4) occasionally progressed to intramucosal carcinoma (category 5), with no instance of invasion into the submucosa or beyond.

Adenoma↗
PubMed2004

Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video).

BACKGROUND AND STUDY AIMS: The narrow band imaging (NBI) system consists of a sequential electronic endoscope system and a source of light equipped with new narrow band filters, yielding very clear images of microvessels on mucosal surfaces. The aim of this prospective study was to measure the correlation between the magnified images obtained with the NBI system and the histological findings, especially with regard to the vascular pattern. In addition, three-dimensional images of microvessels were reconstructed using a laser scanning microscope. PATIENTS AND METHODS: Between July 2001 and August 2003, 165 patients with depressed-type early gastric cancer lesions were enrolled in the study. The lesions were carefully observed with magnification using the NBI system. The images, the pathological characteristics of the lesions, and three-dimensionally reconstructed images of the microvascular networks in biopsied specimens were carefully analyzed. The microvascular patterns were classified into three groups: A, fine network; B, corkscrew; and C, unclassified pattern. The endoscopic images were compared with the histological findings. RESULTS: Of the three types of filter available for use with the NBI system, microvascular formation was best enhanced in B mode images produced using short wavelengths, which focus on the superficial mucosal layer. Among 109 cases of differentiated adenocarcinoma, the group A microvascular pattern was observed in 72 cases (66.1 %). Among 56 cases of undifferentiated adenocarcinoma, the group B pattern was observed in 48 cases (85.7 %; P = 0.0011) The microvascular structure observed using the NBI system corresponded with the superficial mucosal layer in the three-dimensional images obtained using laser scanning microscopy and the resected specimens. CONCLUSIONS: Magnifying endoscopy performed in combination with the NBI system is not sufficient to replace conventional histology, but is capable of predicting the histological characteristics of gastric cancer lesions.

Adenocarcinoma↗
PubMed2003

Energetic protons from a few-micron metallic foil evaporated by an intense laser pulse.

With detailed experimental studies and hydrodynamics and particle-in-cell simulations we investigate the role of the prepulse in laser proton acceleration. The prepulse or pedestal (amplified spontaneous emission) can completely evaporate the irradiated region of a sufficiently thin foil; therefore, the main part of the laser pulse interacts with an underdense plasma. The multiparametric particle-in-cell simulations demonstrate that the main pulse generates the quasistatic magnetic field, which in its turn produces the long-lived charge separation electrostatic field, accelerating the ions.

Journal Article↗
PubMed2003

Activation of defense-related gene expression and systemic acquired resistance in cucumber mosaic virus-infected tobacco plants expressing the mammalian 2'5'oligoadenylate system.

Tobacco plants expressing the mammalian 2'5'oligoadenylate system (2-5A system) exhibit resistance to cucumber mosaic virus (CMV). Here, to characterize the molecular aspect of the resistance to CMV in 2-5A system-expressing tobaccos, the activation of defense-related genes and systemic acquired resistance (SAR) as the markers for the hypersensitive resistance (HR), were elucidated. Northern hybridization analysis indicated that the expression of four pathogenesis-related (PR) protein genes and five HR-related genes were induced in CMV-infected tobaccos expressing 2-5A system. Furthermore, the induction of SAR against Pseudomonas syringae pv. tabaci as second challenge, was observed on CMV-inoculated tobaccos expressing 2-5A system. These results suggested that the resistance to CMV in tobacco expressing 2-5A system is associated with the establishment of an HR-like response.

Adenine Nucleotides↗
PubMed2003

Genetic evolution of alpha fetoprotein producing gastric cancer.

BACKGROUND: Alpha fetoprotein (AFP) producing gastric cancer is an unusual form of aggressive adenocarcinoma with a complex histological picture, including enteroblastic and hepatoid differentiation. AIMS: To investigate the genetic events underlying the phenotypic diversity in AFP producing gastric cancer and the ability of these tumours to produce AFP ectopically. METHODS: Multiple foci from 19 AFP producing gastric adenocarcinomas were microdissected and loss of heterozygosity (LOH) analysis was performed with a panel of microsatellite markers on nine chromosomal arms. RESULTS: For informative cases, LOH was most frequently detected on 17p (100%), followed by 13q (88%), 3p (87%), 5q and 9p (80%), 11q (70%), 18q (58%), 16q (53%), and 8p (50%). The average fractional allelic loss was 0.72. LOH was detected either homogeneously throughout the microdissected foci, or only in some parts of the neoplastic foci for each case. Heterogeneous patterns of LOH indicated genetic progression and/or divergence in clonal evolution. Furthermore, in six cases with heterogeneous LOH of 13q, 13q LOH was restricted to immunohistochemically AFP positive neoplastic foci. CONCLUSION: AFP-GC arises as an aggressive clone with extensive LOH and high fractional allelic loss. The presence of heterogeneous patterns of LOH suggested that the AFP producing carcinoma foci might evolve through genetic progression and/or genetic divergence. Silencing of the crucial gene on 13q may be involved in the acquisition of the AFP producing phenotype.

Adult↗
PubMed2001

Dose and time response after intraamniotic endotoxin in preterm lambs.

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.

Amniotic Fluid↗
PubMed2001

The collagen-like region of surfactant protein A (SP-A) is required for correction of surfactant structural and functional defects in the SP-A null mouse.

Pulmonary surfactant isolated from gene-targeted surfactant protein A null mice (SP-A(-/-)) is deficient in the surfactant aggregate tubular myelin and has surface tension-lowering activity that is easily inhibited by serum proteins in vitro. To further elucidate the role of SP-A and its collagen-like region in surfactant function, we used the human SP-C promoter to drive expression of rat SP-A (rSPA) or SP-A containing a deletion of the collagen-like domain (DeltaG8-P80) in the Clara cells and alveolar type II cells of SP-A(-/-) mice. The level of the SP-A in the alveolar wash of the SP-A(-/-,rSP-A) and SP-A(-/-,DeltaG8-P80) mice was 6.1-and 1.3-fold higher, respectively, than in the wild type controls. Tissue levels of saturated phosphatidylcholine were slightly reduced in the SP-A(-/-,rSP-A) mice compared with SP-A(-/-) littermates. Tubular myelin was present in the large surfactant aggregates isolated from the SP-A(-/-,rSP-A) lines but not in the SP-A(-/-,DeltaG8-P80) mice or SP-A(-/-) controls. The equilibrium and minimum surface tensions of surfactant from the SP-A(-/-,rSP-A) mice were similar to SP-A(-/-) controls, but both were markedly elevated in the SP-A(-/-,DeltaG8-P80) mice. There was no defect in the surface tension-lowering activity of surfactant from SP-A(+/+,DeltaG8-P80) mice, indicating that the inhibitory effect of DeltaG8-P80 on surface activity can be overcome by wild type levels of mouse SP-A. The surface activity of surfactant isolated from the SP-A(-/-,rSP-A) but not the SP-A(-/-,DeltaG8-P80) mice was more resistant than SP-A(-/-) littermate control animals to inhibition by serum proteins in vitro. Pressure volume relationships of lungs from the SP-A(-/-), SP-A(-/-,rSP-A), and SP-A(-/-,DeltaG8-P80) lines were very similar. These data indicate that expression of SP-A in the pulmonary epithelium of SP-A(-/-) animals restores tubular myelin formation and resistance of isolated surfactant to protein inhibition by a mechanism that is dependent on the collagen-like region.

Animals↗
PubMed2001

Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung.

Ventilator-induced lung injury increases proinflammatory cytokines in the adult lung. We asked if positive end-expiratory pressure (PEEP) affects proinflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 +/- 3 d gestation were treated with 100 mg/kg recombinant human surfactant protein-C surfactant and ventilated for 2 or 7 h with 0, 4, or 7 cm H(2)O of PEEP. Unventilated fetal lambs were used as controls. Within 2 h of ventilation, alveolar total protein and activated neutrophils were increased and expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was increased in lung tissue of all ventilated animals relative to unventilated controls. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals than 4 PEEP animals. IL-1beta, IL-6, and IL-8 mRNAs were significantly elevated in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage fractional area of collapsed alveoli was significantly higher for 0 PEEP compared with 4 and 7 PEEP groups. Mechanical ventilation increased the expression of proinflammatory mediators in surfactant-treated preterm lungs and the use of 4 PEEP minimized this response.

Animals↗
PubMed2001

Altered stability of pulmonary surfactant in SP-C-deficient mice.

The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa peptide produced by alveolar epithelial cells in the lung. To discern the role of SP-C in lung function, SP-C-deficient (-/-) mice were produced. The SP-C (-/-) mice were viable at birth and grew normally to adulthood without apparent pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (-/-) mice, nor was mature SP-C protein detected by Western blot of alveolar lavage from SP-C (-/-) mice. The levels of the other surfactant proteins (A, B, D) in alveolar lavage were comparable to those in wild-type mice. Surfactant pool sizes, surfactant synthesis, and lung morphology were similar in SP-C (-/-) and SP-C (+/+) mice. Lamellar bodies were present in SP-C (-/-) type II cells, and tubular myelin was present in the alveolar lumen. Lung mechanics studies demonstrated abnormalities in lung hysteresivity (a term used to reflect the mechanical coupling between energy dissipative forces and tissue-elastic properties) at low, positive-end, expiratory pressures. The stability of captive bubbles with surfactant from the SP-C (-/-) mice was decreased significantly, indicating that SP-C plays a role in the stabilization of surfactant at low lung volumes, a condition that may accompany respiratory distress syndrome in infants and adults.

Animals↗
PubMed2001

Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure.

Pulmonary surfactant protein-D (SP-D) is a member of the collectin family of C-type lectins that is synthesized in many tissues including respiratory epithelial cells in the lung. SP-D is assembled predominantly as dodecamers consisting of four homotrimeric subunits each. Association of these subunits is stabilized by interchain disulfide bonds involving two conserved amino-terminal cysteine residues (Cys-15 and Cys-20). Mutant recombinant rat SP-D lacking these residues (RrSP-Dser15/20) is secreted in cell culture as trimeric subunits rather than as dodecamers. In this study, transgenic mice that express this mutant were generated to elucidate the functional importance of SP-D oligomerization in vivo. Expression of RrSP-Dser15/20 failed to correct the pulmonary phospholipid accumulation and emphysema characteristic of SP-D null (mSP-D-/-) mice. Expression of high concentrations of the mutant protein in wild-type mice reduced the abundance of disulfide cross-linked oligomers of endogenous SP-D in the bronchoalveolar lavage fluid and demonstrated a phenotype that partially overlapped with that of the SP-D-/- mice; the animals developed emphysema and foamy macrophages without the associated abnormalities in alveolar phospholipids typical of SP-D-/- mice. Development of foamy macrophages in SP-D-deficient mice is not secondary to the increased abundance of surfactant phospholipids. Disulfide cross-linked SP-D oligomers are required for the regulation of surfactant phospholipid homeostasis and the prevention of emphysema and foamy macrophages in vivo.

Animals↗
PubMed2001

Antenatal infection/inflammation and postnatal lung maturation and injury.

Chorioamnionitis is frequently associated with preterm deliveries before 30 weeks gestation. Chorioamnionitis correlates both with an increased risk of bronchopulmonary dysplasia and with a decreased risk of respiratory distress syndrome. Both interleukin-1alpha and endotoxin can induce inflammation in the fetal lungs and lung maturation after preterm birth when given by intra-amniotic injection. Inflammation can also result in an arrest of alveolarization, and this lung developmental abnormality is prominent in the lungs of preterm infants that die of bronchopulmonary dysplasia. The mechanisms by which infection/inflammation can have both beneficial and injurious effects on the preterm lung remain to be characterized.

Chorioamnionitis↗
PubMed2001

Biology of surfactant.

Surfactant is a metabolically active assembly of phospholipids and surfactant-specific proteins that is essential for normal lung mechanics. The surfactant proteins SP-A and SP-D also have important innate host defense functions. Surfactant metabolism in the developing lung differs from the adult lung by having slower kinetics of secretion with a longer half-life and more efficient recycling. Ventilation styles that injure the lung also result in altered surfactant function.

Animals↗
PubMed2001

Domains of surfactant protein A that affect protein oligomerization, lipid structure and surface tension.

Surfactant protein A (SP-A) is an abundant protein found in pulmonary surfactant which has been reported to have multiple functions. In this review, we focus on the structural importance of each domain of SP-A in the functions of protein oligomerization, the structural organization of lipids and the surface-active properties of surfactant, with an emphasis on ultrastructural analyses. The N-terminal domain of SP-A is required for disulfide-dependent protein oligomerization, and for binding and aggregation of phospholipids, but there is no evidence that this domain directly interacts with lipid membranes. The collagen-like domain is important for the stability and oligomerization of SP-A. It also contributes shape and dimension to the molecule, and appears to determine membrane spacing in lipid aggregates such as common myelin and tubular myelin. The neck domain of SP-A is primarily involved in protein trimerization, which is critical for many protein functions, but it does not appear to be directly involved in lipid interactions. The globular C-terminal domain of SP-A clearly plays a central role in lipid binding, and in more complex functions such as the formation and/or stabilization of curved membranes. In recent work, we have determined that the maintenance of low surface tension of surfactant in the presence of serum protein inhibitors requires cooperative interactions between the C-terminal and N-terminal domains of the molecule. This effect of SP-A requires a high degree of oligomeric assembly of the protein, and may be mediated by the activity of the protein to alter the form or physical state of surfactant lipid aggregates.

Animals↗
PubMed2001

Multiple minute carcinoids in type A gastritis: attempt at 3-D reconstruction.

In type A gastritis, the numbers of endocrine cell micronests (ECM) and carcinoids increase through the trophic action of gastrin. This study examined the characteristics and growth of carcinoids in type A gastritis. A total of 395 lesions in five surgically removed stomachs with type A gastritis were investigated, in terms of number, size, distribution and histological appearance, to clarify the tumorigenesis and progression of carcinoids. 3-D reconstruction using serial paraffin sections was used to study carcinoid progression. Our findings suggest that in type A gastritis, carcinoids arise in areas where minute carcinoids are present at a high density. They also suggest that early stage carcinoids not only become large expansively, but also develop in a very complex manner, by maintaining contact with surrounding minute carcinoids.

Adult↗