Search PubMed⌕ Search

Biomedical subjects

Y Baba

Publications and source records attributed to Y Baba.

At least 37 records · Page 2Linked to original sources
PubMed2002

Superficial depressed-type cancer monitored by colonoscopy through the early phase of invasion.

Although previous retrospective reports have demonstrated the developmental course of several colorectal tumors, the natural history and progression of depressed carcinoma, especially in the early stage, remains obscure. We report a case of superficial depressed tumor in the transverse colon in a 71-year-old man, which did not change in size and gross configuration through prospective colonoscopic observation over a period of 19 months but which was finally diagnosed as early-stage submucosal invasive cancer. Most depressed cancers have been supposed to arise de novo and grow rapidly, showing aggressive behavior when 10 mm or less in size. However, this case report may suggest that even a depressed tumor may grow to approximately 10 mm within the mucosal layer over a few years and that the growth of colorectal tumors, whether they are polypoid or depressed in configuration, might be fairly slow.

Adenocarcinoma↗
PubMed2001

Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.

Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibitors in which 3-acyltetronic acid is used as a "core" phosphate mimic. A series of novel tetronic acid derivatives were synthesized and evaluated as inhibitors of the dual-specificity protein phosphatases VHR and cdc25B. Several compounds are found to be potent inhibitors of cdc25B, which is a key enzyme for cell-cycle progression. The promising results described herein strongly indicated that this tetronic acid library is potent as a library focused on the PTP/DSP-selective inhibitor.

Cell Cycle Proteins↗
PubMed2001

Induction of SPARC by VEGF in human vascular endothelial cells.

SPARC/osteonectin/BM-40 is a matricellular protein that is thought to be involved in angiogenesis and endothelial barrier function. Previously, we have detected high levels of SPARC expression in endothelial cells (ECs) adjacent to carcinomas of kidney and tongue. Although SPARC-derived peptide showed an angiogenic effect, intact SPARC itself inhibited the mitogenic activity of vascular endothelial growth factor (VEGF) for ECs by the inhibiting phosphorylation of flt-1 (VEGF receptor 1) and subsequent ERK activation. Thus, the role of SPARC in tumor angiogenesis, stimulation or inhibition, is still unclear. To clarify the role of SPARC in tumor growth and progression, we determined the effect of VEGF on the expression of SPARC in human microvascular EC line, HMEC-1, and human umbilical vein ECs. VEGF increased the levels of SPARC protein and steady-state levels of SPARC mRNA in serum-starved HMEC-1 cells. Inhibitors (SB202190 and SB203580) of p38, a mitogen-activated protein (MAP) kinase, attenuated VEGF-stimulated SPARC production in ECs. Since intact SPARC inhibits phosphorylation ERK MAP kinase in VEGF signaling, it was suggested that SPARC plays a dual role in the VEGF functions, tumor angiogenesis, and extravasation of tumors mediated by the increased permeability of endothelial barrier function.

Cells, Cultured↗
PubMed2001

Four tyrosine residues in phospholipase C-gamma 2, identified as Btk-dependent phosphorylation sites, are required for B cell antigen receptor-coupled calcium signaling.

Activation of phospholipase C-gamma2 (PLCgamma2) is the critical step in B cell antigen receptor (BCR)-coupled calcium signaling. Although genetic dissection experiments on B cells have demonstrated that Bruton's tyrosine kinase (Btk) and Syk are required for activating PLCgamma2, the exact activation mechanism of PLCgamma2 by these kinases has not been established. We identify the tyrosine residues 753, 759, 1197, and 1217 in rat PLCgamma2 as Btk-dependent phosphorylation sites by using an in vitro kinase assay. To evaluate the role of these tyrosine residues in phosphorylation-dependent activation of PLCgamma2, PLCgamma2-deficient DT40 cells were reconstituted with a series of mutant PLCgamma2s in which the phenylalanine was substituted for tyrosine. Substitution of all four tyrosine residues almost completely eliminated the BCR-induced PLCgamma2 phosphorylation, indicating that these residues include the major phosphorylation sites upon BCR engagement. Cells expressing PLCgamma2 with a single substitution exhibited some extent of reduction in calcium mobilization, whereas those expressing quadruple mutant PLCgamma2 showed greatly reduced calcium response. These findings indicate that the phosphorylations of the tyrosine residues 753, 759, 1197, and 1217, which have been identified as Btk-dependent phosphorylation sites in vitro, coordinately contribute to BCR-induced activation of PLCgamma2.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2001

Photon-stimulated ion desorption from molybdenum oxides following Mo 2p3/2 excitation.

Photon-stimulated ion desorption from solid MoO3 following the Mo 2p3/2 resonant transition has been investigated. In the XANES spectrum, Mo 2p3/2 peak is split into two components corresponding to the excitations from Mo 2p3/2 into the t2g and e(g) orbitals. It was observed that the desorption yield of O+ ions at the Mo 2p3/2-->e(g) resonance is higher than that at the Mo 2p3/2-->t2g resonance. The Auger decay spectra reveal that there exist two kinds of spectator Auger decays. The high desorption yield at the 2p3/2-->e(g) resonance is interpreted by the fast breaking of the Mo-O bond due to the localization of the electrons in the highly antibonding e(g).

Journal Article↗
PubMed2001

BLNK mediates Syk-dependent Btk activation.

Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been investigated, that of Syk-dependent Btk activation has remained unidentified. We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. This phosphorylation depends on the interaction of Btk and BLNK by means of the Btk-Src homology 2 domain. The existence of such an activation mechanism is supported by the observation that the BCR-induced Btk phosphorylation and activation are significantly reduced in BLNK-deficient B cells as well as in Syk-deficient B cells. Although previous observations have identified the function of BLNK as the linker that integrates the action of Btk and Syk into downstream effectors such as phospholipase Cgamma2, our present study indicates another function of BLNK that connects the activity of Syk to that of Btk.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Asymmetric total synthesis of halicholactone.

The asymmetric total synthesis of the marine metabolite, halicholactone 1, is described. The bisallylic triol 6 with three chiral centers at C8, C12, and C15 was constructed by [2,3]-sigmatropic rearrangement of the sulfoxide 18, which was prepared stereoselectively using the chirality of (diene)Fe(CO)3 complexes. Introduction of the trans-substituted cyclopropane subunit into 21 was successfully achieved using the modified regio- and stereoselective Simmons-Smith reaction. The use of RCM (ring-closing metathesis) methodology (4-->35) was pivotal for the formation of a nine-membered unsaturated lactone fragment of halicholactone 1. As this approach is flexible and stereoselective, other oxylipins could be synthesized by the protocol described herein.

Animals↗
PubMed2001

Field-inversion electrophoresis on a microchip device.

We have proposed a field-inversion electrophoresis on a microchip for a shorter effective length, and investigated the external frequency for the DNA analysis based on the field-inversion electrophoresis device. By using the optimized frequency, we demonstrated that the field-inversion electrophoresis has great potentials for the separation of DNA fragments with shorter effective length.

DNA, Single-Stranded↗
PubMed2001

Direct measurement of conformational changes on DNA molecule intercalating with a fluorescence dye in an electrophoretic buffer solution by means of atomic force microscopy.

By means of atomic force microscopy (AFM), we performed the direct imaging of DNA molecules (200, 500, 1000 bp) in a Tris-borate buffer solution, and measured the contour length and the end-to-end distance of DNA. Processing the data according to the worm-like chain model, we calculated the persistence length of the double-stranded DNA. Based on the analysis of the contour length and the persistence length, we discussed the interactions between DNA and an intercalating fluorescence dye (YO-PRO-1). YO-PRO-1 stacks between the base pairs and extends the contour length of DNA, changing the electric charge and the persistence length of DNA. From AFM measurement, we investigated directly the relationship between the persistence length and the number of the YO-PRO-1 intercalating to DNA. We will discuss on the relationship between the effect of an intercalating dye on the electrophoretic behavior and the conformational changes of DNA with an intercalating dye.

Benzoxazoles↗
PubMed2001

A separation carrier in high-speed proteome analysis by capillary electrophoresis.

We obtained a high-efficiency separation carrier for proteome analysis by capillary electrophoresis. The addition of curdlan or laminaran to the run buffer hastened the migration time without any degradation in resolution. We propose that for the development of the separation carrier it is necessary to synthetically analyze each of the following mobility factors of electroosmotic flow: buffer ionic strength, additional disturbance and adsorption. The total analysis for buffer and additive will be useful for designing high-throughput screening (HTS) systems for proteome analysis without annoying adsorption.

Anions↗
PubMed2001

Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell carcinoma cell lines.

Inostamycin, which was recently isolated from Streptomyces sp. MH816-AF15 as an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, caused a G1-phase accumulation in the cell cycle of small cell lung carcinomas. To investigate whether the cytostatic effect of inostamycin is restricted to lung carcinoma cell lines or applicable to other type of cells, we tested five oral squamous cell carcinoma (SCC) cell lines. Cell growth was suppressed in 62.5--125 ng/ml inostamycin in the culture medium in all oral cancer cell lines tested, with non-viable cells being <1%, indicating inostamycin is cytostatic on SCC cell lines. Decrease in cyclin D1 mRNA and protein expression due to the inostamycin treatment was accompanied by suppression of phosphorylated retinoblastoma susceptibility gene product (pRB-P) levels. Moreover, flow cytometric analysis showed that inostamycin induced an increase in G1/G0 cells (1.2--3.2 fold) over 24 h. These results suggest that inostamycin is a useful agent for tumour dormant cytostatic therapy for oral SCC.

Antineoplastic Agents↗
PubMed2001

Proportional inhibition in the cricket medial giant interneuron.

Inhibitory effects on the number of wind-evoked impulses were studied in the medial giant interneuron of the cricket, Gryllus bimaculatus. The interneuron receives an inhibitory input from wind receptors on cercus ipsilateral to its soma. Using a dual channel wind stimulator, the intensity of inhibitory input was changed over 1,000-fold and effects on the number of spikes were observed. The ipsilateral inhibition reduced the number of outgoing spikes from a level elicited by excitation alone and it did so in proportion to the level of wind responsiveness displayed by each cell. A proportional coefficient of inhibition was derived and its value depended on the level of total excitation of the medial giant interneuron. The medial giant interneurons with high excitation showed a smaller value of the coefficient than those with low excitation. The proportional inhibition of the medial giant interneuron by the ipsilateral cercus suppresses the number of its spikes to a reasonable level for a wide range of stimulus intensities under natural conditions.

Animals↗
PubMed2001

Accumulation of latent transforming growth factor-beta binding protein-1 and TGF beta 1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts.

PURPOSE: To examine immunohistochemically whether extracellular matrix (ECM) of the filtering bleb and of cultured human subconjunctival fibroblasts contains latent TGF beta binding protein-1 (LTBP-1) and TGF beta. METHODS: An enucleated human eye that had undergone trabeculectomy and cultured human subconjunctival fibroblasts were processed for light microscopic immunohistochemistry. Antibodies against LTBP-1, collagen types, fibrillin-1 and TGF beta s were used. TGF beta 1 was located by detecting beta 1-latency associated peptide (LAP). RESULTS: LTBP-1, beta 1-LAP and fibrillin-1 were all located in the subepithelial ECM as well as in the basal epithelial cells of the conjunctiva over the filtering bleb. TGF beta 2 and beta 3 were immunolocated to epithelium and/or fibroblasts/keratocytes. ECM deposited in confluent fibroblast cultures was positive for beta 1-LAP, LTBP-1 and fibrillin-1, whereas sparse cells were negative. CONCLUSIONS: LTBP-1, beta 1-LAP and fibrillin-1 are co-localized to the ECM of the filtering bleb and of cultured conjunctival fibroblasts. Both conjunctival epithelium and fibroblasts are considered to be the source of TGF beta in healing bleb. ECM secreted by in vivo and in vitro subconjunctival fibroblasts may works as a scavenger or repository of TGF beta.

Carrier Proteins↗
PubMed2001

Development of novel biomedicine based on genome science.

Towards the post genomic sequencing era, conventional drug discovery is drastically improving genomic technologies and computational advances. The completion of the entire genome sequence of many experimental organisms as well as the human organism allow us to compare several genomic sequences, comparative genomics, to get valuable information for gene discovery and functional genomics. Pharmacogenomic studies and chemical genomic investigations are quickly becoming fundamental techniques for genomic drug discovery. Additionally, progress in microchip and microarray technology has been stimulating genomic drug discovery studies. This paper reviews recent progress in human genome research, basic elements in the new strategy for drug discovery based on genome science, and future perspectives for the bio and pharmaceutical industries.

Computational Biology↗
PubMed2001

Enhanced throughput for DNA sequencing by capillary array electrophoresis with a gradient of electric field strength.

The effect of electric field gradients are examined on the speed, selectivity, read length, and accuracy for DNA sequencing using capillary array electrophoresis. Modified electric field gradients was realized to read over 800 bases within 140 min. The method developed is effectively applicable to single nucleotide polymorphism analysis for genomic drug discovery and pharmacogenomics.

Electrophoresis, Capillary↗
PubMed2001

Apoptosis of periodontal ligament cells induced by mechanical stress during tooth movement.

The mechanical force generated during tooth movement creates compressed and cell-free areas in the periodontal membrane. The way in which periodontal ligament cells disappear at the compressed area during tooth movement remains unclear. In the present study we examined whether periodontal ligament cells undergo apoptosis by mechanical stress during tooth movement using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end-labelling method (TUNEL). TUNEL-positive stainings of periodontal ligament cells began to appear at the compressed areas 12 h after tooth movement, and the number of those cells reached maximum at 24 h after tooth movement. Thereafter TUNEL-positive cells disappeared at 48 h, and direct and undermining bone resorption began at the same area 72 h after tooth movement. These results showed that compressed periodontal ligament cells were eliminated by apoptosis in the early phase of tooth movement.

Alveolar Bone Loss↗