Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 73 records · Page 4Linked to original sources

PubMed2001

Two types of MGDG synthase genes, found widely in both 16:3 and 18:3 plants, differentially mediate galactolipid syntheses in photosynthetic and nonphotosynthetic tissues in Arabidopsis thaliana.

In Arabidopsis, monogalactosyldiacylglycerol (MGDG) is synthesized by a multigenic family of MGDG synthases consisting of two types of enzymes differing in their N-terminal portion: type A (atMGD1) and type B (atMGD2 and atMGD3). The present paper compares type B isoforms with the enzymes of type A that are known to sit in the inner membrane of plastid envelope. The occurrence of types A and B in 16:3 and 18:3 plants shows that both types are not specialized isoforms for the prokaryotic and eukaryotic glycerolipid biosynthetic pathways. Type A atMGD1 gene is abundantly expressed in green tissues and along plant development and encodes the most active enzyme. Its mature polypeptide is immunodetected in the envelope of chloroplasts from Arabidopsis leaves after cleavage of its transit peptide. atMGD1 is therefore likely devoted to the massive production of MGDG required to expand the inner envelope membrane and build up the thylakoids network. Transient expression of green fluorescent protein fusions in Arabidopsis leaves and in vitro import experiments show that type B precursors are targeted to plastids, owing to a different mechanism. Noncanonical addressing peptides, whose processing could not be assessed, are involved in the targeting of type B precursors, possibly to the outer envelope membrane where they might contribute to membrane expansion. Expression of type B enzymes was higher in nongreen tissues, i.e., in inflorescence (atMGD2) and roots (atMGD3), where they conceivably influence the eukaryotic structure prominence in MGDG. In addition, their expression of type B enzymes is enhanced under phosphate deprivation.

Amino Acid Sequence↗

PubMed2001

Monitoring of methyl jasmonate-responsive genes in Arabidopsis by cDNA macroarray: self-activation of jasmonic acid biosynthesis and crosstalk with other phytohormone signaling pathways.

Jasmonates mediate various physiological events in plant cells such as defense responses, flowering, and senescence through intracellular and intercellular signaling pathways, and the expression of a large number of genes appears to be regulated by jasmonates. In order to obtain information on the regulatory network of jasmonate-responsive genes (JRGs) in Arabidopsis thaliana (Arabidopsis), we screened 2880 cDNA clones for jasmonate responsiveness by a cDNA macroarray procedure. Since many of the JRGs reported so far have been identified in leaf tissues, the cDNA clones used were chosen from a non-redundant EST library that was prepared from above-ground organs. Hybridization to the filters was achieved using alpha-33P-labeled single-strand DNAs synthesized from mRNAs obtained from methyl jasmonate (MeJA)-treated and untreated Arabidopsis seedlings. Data analysis identified 41 JRGs whose mRNA levels were changed by more than three fold in response to MeJA. This was confirmed by Northern blot analysis by using eight representatives. Among the 41 JRGs identified, 5 genes were JA biosynthesis genes and 3 genes were involved in other signaling pathways (ethylene, auxin, and salicylic acid). These results suggest the existence of a positive feedback regulatory system for JA biosynthesis and the possibility of crosstalk between JA signaling and other signaling pathways.

Acetates↗

PubMed2001

Accumulation of plant galactolipid affects cell morphology of Escherichia coli.

Monogalactosyldiacylglycerol (MGDG) is a major constituent of thylakoid membrane in chloroplasts. Therefore, it is considered to have an important role in the maintenance of the complicated structure of the thylakoid membrane. We have succeeded in cloning the enzyme for MGDG synthesis and overexpressed it in Escherichia coli. In this study we analyzed the morphology of the E. coli harboring the gene. The fatty acid composition of its membrane lipids did not differ between the wild type and transformant, except for the appearance of MGDG. However, transformant cells appeared to be elongated. DAPI staining revealed the entire intracellular region of filamentous cells to be stained; therefore, the elongation of the cells is probably due to a defect in cell division. Atomic force microscopy revealed that the transformant had a smooth but scratched surface. It was concluded that the excessive accumulation of a non-bilayer lipid, MGDG, interfered with the translocation of proteins across the plasma membrane, including those for cell division.

Escherichia coli↗

PubMed2001

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS: S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The patients who achieved a partial or complete response to chemoradiotherapy showed significantly less S-VEGF than those patients who were nonresponders (P = 0.018). A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus.

Adult↗

PubMed2001

Elucidation of the differences between the 430- and 455-nm absorbing forms of P450-isocyanide adducts by resonance Raman spectroscopy.

Alkylisocyanide adducts of microsomal P450 exist in two interconvertible forms, each giving the Soret maximum around 430 or 455 nm. This is demonstrated with a rabbit liver P450 2B4. Resonance Raman spectra of the 430- and 455-nm forms were examined for typical P450s of the two types as well as for P450 2B4 because the 430-nm form of P450 2B4 is liable to change into P420. P450cam and P450nor were selected as a model of the 430- and 455-nm forms, respectively. For the n-butyl isocyanide (CNBu) adduct, the Fe(II)-CNBu stretching band was observed for the first time at 480/467 cm(-1) for P450cam and at 471/459 cm(-1) for P450nor with their (12)CNBu/(13)CNBu derivatives. For P450cam, but not P450nor, other (13)C isotope-sensitive bands were observed at 412/402, 844/835, and 940/926 cm(-1). The C-N stretching mode was identified by Fourier transform IR spectroscopy at 2116/2080 cm(-1) for P450cam and at 2148/2108 cm(-1) for P450nor for the (12)C/(13)C derivatives. These findings suggest that the binding geometry of isocyanide differs between the two forms-bent and linear structures for P450cam-CNBu and P450nor-CNBu, respectively. In contrast, in the ferric state, the Raman (13)C isotopic frequency shifts, and the IR C-N stretching frequencies (2213/2170 and 2215/2172 cm(-1)) were similar between P450cam and P450nor, suggesting similar bent structures for both.

Animals↗

PubMed2001

Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin.

Increased expression of plasminogen activator inhibitor-1 (PAI-1) in cancer patients is associated with unfavorable outcome, and the reason for this paradox has been poorly understood. We have previously reported elevated levels of PAI-1 in primary tumors of advanced neuroblastomas (Y. Sugiura et al., Cancer Res., 59: 1327-1336, 1999). Here we demonstrate that PAI-1 is coexpressed with the angiogenesis marker alpha(v)beta3 integrin in blood vessels of primary neuroblastoma tumors, suggesting that PAI-1 plays a role in angiogenesis. Using human brain microvascular endothelial cells (HBMECs), we found that PAI-1 inhibits alpha(v)beta3 integrin-mediated cell adhesion to vitronectin but promotes alpha5beta1-mediated migration from vitronectin toward fibronectin. Inhibition of vitronectin adhesion by PAI-1 did not induce HBMEC apoptosis. PAI-1 also inhibited endothelial tube formation on Matrigel in the presence of vitronectin but had a stimulatory effect in the presence of fibronectin. This effect of PAI-1 on microvascular endothelial cells is primarily related to the ability of PAI-1 to bind to vitronectin via its NH2-terminal domain and to interfere with cell adhesion to vitronectin. We propose that PAI-1 acts as a positive switch for angiogenesis by promoting endothelial cell migration away from their vitronectin-containing perivascular space toward fibronectin-rich tumor tissue. These observations provide a novel explanation for the enhancing effect of PAI-1 in cancer progression.

Apoptosis↗

PubMed2001

Mobilization of transposons by a mutation abolishing full DNA methylation in Arabidopsis.

A major component of the large genomes of higher plants and vertebrates comprises transposable elements and their derivatives, which potentially reduce the stability of the genome. It has been proposed that methylation of cytosine residues may suppress transposition, but experimental evidence for this has been limited. Reduced methylation of repeat sequences results from mutations in the Arabidopsis gene DDM1 (decrease in DNA methylation), which encodes a protein similar to the chromatin-remodelling factor SWI2/SNF2 (ref. 7). In the ddm1-induced hypomethylation background, silent repeat sequences are often reactivated transcriptionally, but no transposition of endogenous elements has been observed. A striking feature of the ddm1 mutation is that it induces developmental abnormalities by causing heritable changes in other loci. Here we report that one of the ddm1-induced abnormalities is caused by insertion of CAC1, an endogenous CACTA family transposon. This class of Arabidopsis elements transposes and increases in copy number at high frequencies specifically in the ddm1 hypomethylation background. Thus the DDM1 gene not only epigenetically ensures proper gene expression, but also stabilizes transposon behaviour, possibly through chromatin remodelling or DNA methylation.

Arabidopsis↗

PubMed2001

Synchronous scanning of undulator gap and monochromator for XAFS measurements in soft x-ray region.

Synchronous scanning of the undulator gap and a monochromator was done to obtain smooth profiles of incident x-rays that are suitable for XAFS measurements. By changing the gap from 150 mm(B=0.12 T) to 140 mm (B=0.15 T) with the use of the 3rd to 11th harmonic peaks, soft x-rays with energy from 200 eV to 1200 eV were obtained. The smooth profile of the incident x-rays provided high-quality measurement of XANES and EXAFS spectra in the soft x-ray region. Issues that would improve the synchronous scanning system are discussed.

Journal Article↗

PubMed2001

In situ XAFS analysis system for high-pressure catalytic reactions and its application to CO2 hydrogenation over a Rh/Y-zeolite catalyst.

An in-situ XAFS cell was developed and used for the structural analysis of a Rh ion-exchanged zeolite catalyst during high-pressure hydrogenation of carbon dioxide. The in-situ cell enabled analyses of the catalyst structures that changed with the reaction atmosphere and elapsed time; the peak assigned to Rh-O scattering changed to that assigned to Rh-Rh scattering at 404 K during the pretreatment by hydrogen. After 30 min. of the carbon dioxide hydrogenation reaction, the peak intensity assigned to Rh-Rh scattering increased corresponding to the increase in the catalytic activity.

Journal Article↗

PubMed2001

Multi-component fitting XAFS analysis of molybdate species during catalyst preparation ration by the molten salt method.

The goal of the present study was to elucidate the formation mechanisms of highly dispersed catalysts by the molten salt method. For this purpose, multi-component fitting Mo K-edge EXAFS analysis was applied to the structure of molybdate catalysts prepared in KNO3 and NaNO3. The analysis revealed that MoO3 dissolved in molten salts was at first transformed into polymolybdate anions and finally into MoO(4)2- anions. The transformation into MoO(4)2- anions took place at a lower temperature when NaNO3 was used as molten salt than KNO3. In contrast, polymolybdate anions were stable even at higher temperature when ZrO2 was added as a support of molybdate.

Journal Article↗

PubMed2001

4d Electronic structure analysis of ruthenium in the perovskite oxides by Ru K- and L-edge XAS.

The 4d electronic structure of ruthenium in the perovskite oxides, La2MRuIVO6 (M = Zn, Mg, and Li) and Ba2YRuVO6, has been investigated by the Ru K-and L-edge XANES and EXAFS analyses. Such X-ray absorption spectroscopic results clarify that the RuIV (d4) and RuV (d3) ions are stabilized in nearly regular Oh site. Comparing the Ru L-edge XANES spectra of perovskites containing isovalent ruthenium, it has been found that the t2g state is mainly influenced by A site cation, whereas the eg is mainly affected by neighboring B site cation. The experimental EXAFS spectra in the range of R < or = approximately 4.5 A are well reproduced by ab-initio calculation based on crystallographic data, which supports the long-range structure presented by Rietveld refinement.

Journal Article↗

PubMed2001

XAFS study on the sulfidation mechanisms of Co-Mo catalysts supported on activated carbon and alumina: effect of complexing agent.

The effect of nitrilotriacetic acid (NTA) as a complexing agent on the sulfidation mechanisms of Co-Mo catalysts supported on activated carbon and alumina was examined by the XAFS technique. The XAFS results revealed that NTA interacted with Co atoms and formed the Co-NTA interaction, while it showed almost no influence on the local structures around Mo atoms. The Co-NTA interaction suppressed the aggregation of cobalt atoms and the interaction between cobalt and alumina during sulfiding, and consequently promoted the formation of the Co-Mo-S phase.

Journal Article↗

PubMed2001

Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays.

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.

Animals↗

PubMed2001

Biological aspects of neuroblastomas identified by mass screening in Quebec.

BACKGROUND: Neuroblastoma has several characteristics that suggest that preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the 5-yr period, 45 tumors were detected by screening, 20 were identified clinically prior to the third week, and 64 were identified clinically at a later time. We analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2 of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin. All of these patients are alive and well. The 20 patients detected prior to the 3-week screen had similar biological characteristics. In contrast, of the patients detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference between the screened and clinically detected cases was highly significant for each biological variable. Preliminary data on other biological variables, such as neurotrophin expression and allelic loss on 1 p in these patients are consistent with the above findings. These data suggest that mass screening for neuroblastoma at or before 6 months of age detects almost exclusively tumors that have favorable biological characteristics, many of which might have regressed spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is unlikely to accomplish its intended goal, and should probably be discontinued.

Age Factors↗

PubMed2001

Evaluation of the rodent micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS)-Mammalian Mutagenicity Study Group (MMS).

To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

Animals↗

PubMed2001

Inhibition of osteoclast differentiation and bone resorption by cathepsin K antisense oligonucleotides.

We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer.

Animals↗

PubMed2001

Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies-a report from the Children's Cancer Group Study.

BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic neurologic syndrome affecting 2-3% of children with neuroblastoma. Although children with OMA and neuroblastoma may have higher survival, many experience a significant amount of late neurologic impairment, which may be immunologically mediated. The aim of this study was to compare the outcome of neuroblastoma patients with and without OMA, relating to prognostic factors, treatment, and the presence or absence of anti-neuronal antibodies. PROCEDURE: Questionnaires were mailed out requesting information on the current neurologic status of patients who submitted sera at diagnosis to the Children's Cancer Group serum bank from 1980 to 1994. Information was requested on clinical and biological patient characteristics as well as clinical aspects of the patients identified as having OMA syndrome, including presentation and treatment for OMA, late sequelae of OMA, the presence or absence of antineuronal antibodies, and survival. Sera from 16 of the OMA patients and 48 case-controls with neuroblastoma were assayed for anti-neuronal antibodies. RESULTS: Of the 675 responses received, 21 patients had OMA. Ninety percent of OMA patients presented with non-metastatic disease, vs. 35% of non-OMA patients. Estimated 3-year survival for the OMA patients with nonmetastatic disease (stage I, II, III) greater than 1 year of age was 100% vs. 77% for similar non-OMA patients (P = 0.0222). At follow-up, 14/19 evaluable OMA patients displayed some form of developmental or neurologic abnormality. There was no significant correlation of late sequelae with antineuronal antibodies, age, time between OMA symptoms and diagnosis, or treatment given for tumor or OMA. There was a significant correlation of late sequelae with lower stage disease (I and II) compared to more advanced disease (III and IV). CONCLUSIONS: Patients with OMA and neuroblastoma have excellent survival but a high risk of neurologic sequelae. Favorable disease stage correlates with a higher risk for development of neurologic sequelae. The role of anti-neuronal antibodies in late sequelae of OMA needs further clarification.

Adolescent↗

PubMed2001

Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: histopathologic features-a report from the Children's Cancer Group.

BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic syndrome that occurs in about 2-3% of all cases of neuroblastoma. The histopathologic characteristics of neuroblastoma tumors associated with this syndrome were evaluated in a series of cases and controls. PROCEDURE: Pathology slides from a total of 54 neuroblastoma tumors were reviewed blindly. They included 13 tumors associated with opsoclonus-myoclonus and 41 age- and stage-matched controls. All tumors were classified into either the favorable (FH) or unfavorable histology (UH) group according to the International Neuroblastoma Pathology Classification (the Shimada system). Grade of lymphocytic infiltration was evaluated and presence or absence of lymphoid follicles was recorded in the individual tumor tissues. RESULTS: Twelve of 13 cases with opsoclonus-myoclonus were in the FH group. Twelve of 13 cases had diffuse (found in every section prepared from the multiple portions of the primary tumor) and extensive (occupying more than 50% of a single of multiple microscopic fields with x 100 magnification) lymphocytic infiltration with lymphoid follicles. Of the 41 control cases (27 FH and 14 UH tumors), 18 had focal areas of lymphocytic infiltration and six showed lymphoid follicles, but none had diffuse or extensive infiltration in their primary tumors. CONCLUSIONS: Diffuse and extensive lymphocytic infiltration with lymphoid follicles is a characteristic histologic feature of neuroblastic tumors with opsoclonus-myoclonus. This observation suggests an immune-mediated mechanism for this rare paraneoplastic syndrome.

Adolescent↗