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Biomedical subjects

M Oshima

Publications and source records attributed to M Oshima.

At least 55 records · Page 3Linked to original sources
PubMed1999

Expression of the H type 1 blood group antigen during enterocytic differentiation of Caco-2 cells.

We made a comparative study of the structures of the oligosaccharides on the glycoproteins from Caco-2 human colonic adenocarcinoma cells, before and after differentiation. Enterocytic differentiated Caco-2 cells highly express H type 1 blood group antigen on the cell surface as well as activities of brush border membrane hydrolases, such as dipeptidyl peptidase IV and alkaline phosphatase. A strong correlation was observed between the amounts of H type 1 blood group antigen and the degrees of differentiation. Structural analysis with use of lectin affinity high performance liquid chromatography revealed that typical mucin-type sugar chains of the glycoproteins from undifferentiated cells have H type 2 group, linear polylactosamines, and core 1 structure. On the other hand, differentiated cells newly contain H type 1 and Le(b) groups and core 2 structure. Mucins with H type 1 group make contact with brush border membrane enzymes on differentiated cells. Furthermore benzyl 2-acetamide-2-deoxy-alpha-D-galactopyranoside inhibited both expression of H type 1 group on the cell surface and enhancement of brush border membrane enzyme activities even in the presence of a differentiating inducer. These results suggest that the mucin-type sugar chains with H type 1 group have important functions regarding differentiation of Caco-2 cells.

ABO Blood-Group System↗
PubMed1999

Cell membrane dynamics and the induction of apoptosis by lipid compounds.

To investigate the induction of apoptosis by some lipid compounds which are a potent inducer of apoptosis, the plasma membrane fluidity of U937 cells was measured using the fluorescent probe, pyrene. The increase of the membrane fluidity was observed immediately after the treatment of cells with lipid inducers. We also found that the trigger of apoptosis was pulled within 30 min after treatment. Data from the dynamic light scattering experiment indicated that lipid inducers were dissolved to form the emulsion. At the very early stage of apoptosis, possibly, the well-controlled transfer of lipid inducers from the emulsion to the lipid layer of cells can bring about the increase of membrane dynamics which might lead to the induction of apoptosis.

Apoptosis↗
PubMed1999

Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases.

To determine the role of C-C chemokines in the pathogenesis of granulomatous lung diseases, we studied the mRNA levels of C-C chemokines, regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 in bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis (n = 17), hypersensitivity pneumonitis (HP) (n = 4), and cryptogenic fibrosing alveolitis (CFA) (n = 10) using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The mRNA levels of RANTES, MIP-1alpha, and MIP-1beta in BAL cells were significantly correlated with the lavaged lymphocyte proportion, and a significant inverse correlation was observed between the mRNA level of MIP-1beta and the CD4/CD8 ratio of lavaged lymphocytes. Among the three diseases, the mRNA levels of RANTES and MIP-1alpha were significantly higher in the patients with sarcoidosis or HP compared with those in the patients with CFA. The level of MIP-1beta mRNA was significantly higher in the HP patients compared with that in the patients with sarcoidosis or CFA. No significant differences were observed in the level of MCP-1 mRNA among the three diseases. Thus, RANTES and MIP-1alpha were suggested to be important in the pathogenesis of granulomatous inflammation in sarcoidosis and HP. MIP-1beta might play an important role in the pathogenesis of HP, mediating the recruitment of lymphocytes specific to HP.

Adult↗
PubMed1999

Phospholipid turnover in the inflamed intestinal mucosa: arachidonic acid-rich phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease.

Cytosolic phospholipase A2 (PLase A2) is activated by low Ca2+ concentrations and translocates from the cytosol to the cell membrane, releasing arachidonic acid; the arachidonic acid cascade then leads to the production of many inflammatory mediators. The aim of this study, accordingly, was to investigate the role of phospholipid metabolism in the intestinal mucosa in inflammatory bowel disease (IBD). Surgically resected specimens from patients with Crohn's disease (CD), ulcerative colitis (UC), and colrectal cancer (non-cancerous tissue; as a control) were submitted to phospholipid analysis and a PLase A2 assay, which measures the degradation of endogenous mucosal phospholipids. A high percentage of plasmenylethanolamine (plas.E) was detected in the glycerophospholipid fraction of CD mucosa. The arachidonic acid content of the phosphatidylethanolamine plus plas.E subfraction was higher in inflamed than in intact mucosa in CD. PLaseA2 activity, resulting in lysophosphatidyl ethanolamine production, was detected only in inflamed mucosa from CD and UC patients, but not in normal mucosa from controls. PLaseA2 activity was highest in moderately inflamed mucosa adjacent to a severely ulcerated area. The PLaseA2 that reacts with endogenous phosphatidylcholine (PC) to form lysoPC was found irrespective of the presence of inflammation. The PLaseA2 that reacts with ethanolamine-containing phospholipids is more closely related to inflammation than other PLaseA2 isoenzymes in IBD mucosa.

Adult↗
PubMed1999

Serum fatty acid composition as a marker of eating habits in normal and diabetic subjects.

It is known that the Japanese people have had healthy eating habits, which may explain their low incidence of non-insulin-dependent diabetes mellitus (NIDDM). In the present study, in order to examine dietary habits such as fish consumption, the serum fatty acids from 190 normal people in their 30s and 50s living in Tokyo were surveyed. Furthermore, the fatty acid composition of 44 patients with DM was studied to clarify the difference in eating habits between normal and diabetic patients. The n-3:n-6 ratio of polyunsaturated fatty acids was 0.19 +/- 0.05 for the group in their 30s and 0.27 +/- 0.08 for the group in their 50s (P < 0.01). In patients with DM, the n-3:n-6 ratio was 0.23 +/- 0.05 and glycosylated haemoglobin (HbA1c) was 6.52 +/- 0.55%. After 4 months of dietary education, the n-3:n-6 ratio had increased to 0.27 +/- 0.06 (P < 0.01) and HbA1c had decreased significantly to 6.16 +/- 0.35% (P < 0.01). These findings indicated that people in their 50s tend to eat a traditional diet, which is abundant in fish oil, whereas people in their 30s, as well as patients with NIDDM in their 50s, appear to eat a diet that includes less fish than the traditional diet. Benefits of fish oil have been reported to be limited due to adverse effects in the glycemic controls in patients with NIDDM. Early instruction of newly diagnosed patients to encourage them to change their eating habits to a more traditional diet, which is abundant in fish, proved to be one of the safe methods for interventions in patients with DM.

Adult↗
PubMed1999

Impaired extrapyramidal function caused by the targeted disruption of retinoid X receptor RXRgamma1 isoform.

BACKGROUND: Retinoid X receptors RXRalpha, beta and gamma exert multiple functions in the genetic regulation of mammalian signalling systems by forming heterodimeric complexes with several nuclear ligand receptors. In contrast to the widespread expression of RXRalpha and RXRbeta, the expression of RXRgamma is restricted to particular tissues in which RXRgamma1 is the major isoform expressed in the mouse corpus striatum. RESULTS: To investigate the function of this particular isoform RXRgamma1, we generated RXRgamma1 gene-knockout mice by homologous recombination in ES cells. Both heterozygous and homozygous mice showed severe runting after birth, which often resulted in the early death of mice of the 129/C57BL-6 genetic background. Independent of genetic background, however, the expression of choline acetyltransferase (ChAT) in the cholinergic interneurones in the striatum (caudal putamen) was markedly reduced in the RXRgamma1 gene-null mice. Furthermore, the mutant exhibited an altered response to the administration of dopamine receptor antagonists, haloperidol and chlorpromazine, which normally induce catalepsy in mice. CONCLUSIONS: These results strongly suggest that RXRgamma1 plays an important role in either the development or activation of cholinergic neurones in nigrostriatal extrapyramidal pathways.

Animals↗
PubMed1999

Pre-operative localization and tissue uptake study in parathyroid imaging with technetium-99m-sestamibi.

BACKGROUND: The diagnostic ability of 99mTc-sestamibi was compared with other techniques and the mechanism of parathyroid uptake was investigated. METHODS: Double-phase 99mTc-sestamibi scanning was performed in 52 primary and 28 renal hyperparathyroidism patients. Gene expressions of mdr1 and mrp were examined by reverse transcriptase polymerase chain reaction in parathyroid tissue. RESULTS: The sensitivity of 99Tc-sestamibi in primary and renal hyperparathyroidism was 91% and 75%, respectively, higher than for ultrasonography, T1/Tc subtraction scintigraphy, or computed tomography. Early 99mTc-sestamibi uptake was washed out in delayed images in 7% and 30% of glands in primary and renal hyperparathyroidism, respectively. Expression of mdr1 and mrp mRNA was found in 5 of 23 and 16 of 31 glands, respectively, and their expression correlated with washout in delayed images. CONCLUSION: 99mTc-sestamibi was the best localization test. mdr1 and mrp were associated with 99Tc-sestamibi washout, but their role in the parathyroid remains unclear.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

High prevalence of Epstein-Barr virus type A strain with the 30 b.p. deletion of the latent membrane protein-1 gene in a Japanese population.

BACKGROUND: The pathogenic activity of Epstein-Barr virus (EBV) with a characteristic 30 b.p. deletion of the latent membrane protein-1 (LMP-1) gene is controversial. We analyzed the LMP-1 gene and two major strains of EBV, type A and type B, in Japanese patients with EBV-associated disease. METHODS: We directly sequenced the carboxy terminal part of the LMP-1 gene from 15 EBV-infected patients; 10 patients with infectious mononucleosis (IM) and one patient each with Hodgkin's disease, B cell lymphoma, Wiskott-Aldrich syndrome (WAS), AIDS and atypical EBV infection (atEBV). The EBV subtype was studied by determining the 3' divergence of Epstein-Barr virus nuclear antigen (EBNA)-2 using polymerase chain reaction primers. RESULTS: Twelve of 15 patients had EBV with the 30 b.p. deletion and numerous point mutations of the LMP-1 gene, regardless of the disease. Two patients, one with IM and one with WAS, had EBV without the 30 b.p. deletion. One patient with atEBV had two types of LMP-1 gene, one with and one without the 30 b.p. deletion. Thirteen patients had EBV type A, the WAS patient had the type B strain and the atEBV patient had both types A and B. In the patient with atEBV, the two types of LMP-1 gene and two EBV subtypes were detected simultaneously. CONCLUSIONS: The characteristic 30 b.p. deletion of the LMP-1 gene is not an important factor in the pathogenesis of EBV-associated diseases. The EBV type A strain with the 30 b.p. deletion of the LMP-1 gene is prevalent in the Japanese population.

Epstein-Barr Virus Infections↗
PubMed1999

[Infant leukemia with t(1;22) presenting proliferation of erythroid and megakaryocytic cell lineages].

We report a case of infant leukemia with the proliferation of both erythroblast and megakaryoblast lineages. The blasts became double-positive for both erythroblastic and megakaryoblastic surface markers at the time of bone marrow relapse. A 9-month-old girl was admitted to our hospital presenting chiefly poor with weight gain and anemia. She also had splenomegaly, pleural effusion, leukocytosis, and thrombocytopenia. A bone marrow specimen showed 53.2% erythroblasts (PAS positive, alpha-NA positive, CD41 negative, MPO negative) and 20.4% megakaryoblasts with marked cytoplasmic blebs. We examined specimens by two-color flow cytometric analysis. At the onset, CD41+ glycophorin A- fraction and CD41- glycophorin A+ fraction were two major components. At the bone marrow relapse, the majority of blasts had altered to double-positive. Chromosomal analysis showed t (1; 22) (p13; q13), which has been reported to be specific for acute megakaryoblastic leukemia (M7) in infants. We reasoned that a leukemia had occurred in this patient at a progenitor cell level common to both erythroid and megakaryocytic lineages.

Bone Marrow Cells↗
PubMed1999

Structure, activity, and immune (T and B cell) recognition of botulinum neurotoxins.

Botulism, which was first reported over a century ago, is caused by botulinum neurotoxins produced by Clostridium botulinum in seven immunological serotypes (A through G). The primary structures of a number of these BoNTs have been determined and are reviewed here, together with their gene structure and synthesis. The biological actions of BoNTs, which result in their ability to block neurotransmitter release have been the subject of intensive study, and in this review we discuss the binding of BoNTs to the cell surface as well as the mechanism of their intercellular action. The ability of BoNTs to block neurotransmitter release has been exploited in therapeutic applications to reduce muscle hyperactivity for the treatment of a variety of clinical conditions associated with involuntary muscle spasm and contractions. The advantages, limitations, and risks of these applications are discussed. Certain compounds provide some limited protection against BoNT. However, more effective protection has been obtained immunologically either by passive immunity (i.e., by administration of anti-BoNT Abs) or by immunization with inactivated toxin. More recently, excellent protection has been obtained by immunization with the receptor-binding region comprising the C-terminal (residues 860 to 1296) fragment (Hc) of the heavy chain of BoNT/A. Here we review the mapping of the epitopes on the Hc region of BoNT/A that are recognized by anti-BoNT/A Abs raised in horse, human, and mouse. The epitopes on the Hc that are recognized by anti-Hc Abs and by Hc-primed T lymphocytes were mapped in two mouse strains [BALB/c (H-2d) and SJL (H-2s)]. The peptides, which contain Ab or T cell epitopes (or both) on the Hc, were used as immunogens in BALB/c and SJL mice and we identified those peptides whose Ab and/or T-cell response cross-react with Hc. Identification of these peptides is an important first step in the intricate requirements for the design of a synthetic vaccine.

Amino Acid Sequence↗
PubMed1998

Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout mice.

Transforming growth factor (TGF)-beta receptor type II gene (Tgfbr2) knockout and wild type mice underwent chronic estrogen exposure using estradiol pellets. Histological examination of the pituitary glands found 38 adenomas in 14 Tgfbr2(+/-) mice but only one tumor in ten wild type mice. Pituitary tumorigenesis is greatly accelerated in Tgfbr2(+/-) mice by estrogen treatment.

Adenoma↗
PubMed1998

Submicrometre-area high-energy-resolution photoelectron spectroscopy system.

A submicrometre-area photoelectron spectroscopy system that uses a multi-layer-coated Schwarzschild objective as the soft X-ray microbeam optics has been developed. The system is located at an undulator beamline (BL-16U) at the Photon Factory in the High Energy Accelerator Research Organization. By knife-edge measurement, the microbeam size was estimated to be 160 nm at the sample position using a 25-75% criterion. Photoelectron spectral measurements revealed that the Fermi edge width was 0.12 eV, which means that the instrumental resolution was 0.05 eV, after removing the natural broadening of the Fermi edge at room temperature. This system offers both high energy resolution and high spatial resolution.

Journal Article↗
PubMed1998

Real-time analysis for MBE by time-resolved core-level photoelectron spectroscopy.

A system has been developed for the real-time analysis of surface reactions during molecular beam epitaxial growth which uses photoelectron spectroscopy with VUV light taken from synchrotron radiation. This system consists of a synchrotron radiation beamline and growth/analysis apparatus in which photoelectron spectroscopy is performed with sub-second time resolution. In this system, photoelectron spectra are measured in sequence by a 'non-scanning' measurement method that enables the acquisition of snapshot photoelectron spectra using a multi-channel detector. This non-scanning measurement method was enabled by equipping an electric field correction grid. This system was used to monitor the photoelectron spectra of a GaSb(001) surface.

Journal Article↗
PubMed1998

Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes.

The DPC4 (SMAD4) gene plays a key role in the TGFbeta signaling pathway. We inactivated its mouse homolog Dpc4 (Smad4). The homozygous mutants were embryonic lethal, whereas the heterozygotes showed no abnormality. We then introduced the Dpc4 mutation into the Apc(delta716) knockout mice, a model for human familial adenomatous polyposis. Because both Apc and Dpc4 are located on chromosome 18, we constructed compound heterozygotes carrying both mutations on the same chromosome by meiotic recombination. In such mice, intestinal polyps developed into more malignant tumors than those in the simple Apc(delta716) heterozygotes, showing an extensive stromal cell proliferation, submucosal invasion, cell type heterogeneity, and in vivo transplantability. These results indicate that mutations in DPC4 (SMAD4) play a significant role in the malignant progression of colorectal tumors.

Adenocarcinoma↗
PubMed1998

Dihydroheptaprenyl and dihydrodecaprenyl monophosphates induce apoptosis mediated by activation of caspase-3-like protease.

Dolichyl phosphate, an essential carrier lipid in the biosynthesis of N-linked glycoprotein, has been found to induce apoptosis in rat glioma C6 cells and human monoblastic leukemia U937 cells. In the present study, dolichyl phosphate and structurally related compounds were examined regarding their apoptosis-inducing activities in U937 cells. Dihydroheptaprenyl and dihydrodecaprenyl phosphates, of which isoprene units are shorter than that of dolichyl phosphate, induced apoptosis in U937 cells. This phenomenon occurred in a dose- and time-dependent manner, as seen with dolichyl phosphate-induced apoptosis. Derivatives of the same isoprene units of dolichyl phosphate, such as dolichol, dolichal or dolichoic acid, did not induce DNA fragmentation. Farnesyl phosphate and geranylgeranyl phosphate also failed to induce apoptosis. During apoptosis, the caspase family of cysteine proteases play important roles. We observed that apoptosis induced by dihydroprenyl phosphate was mediated by caspase-3-like (CPP32-like) activation but not by caspase-1-like (ICE-like) activation. This caspase-3-like activation was inhibited by a specific inhibitor of caspase-3, DEVD-CHO, but not by an caspase-1 inhibitor YVAD-CHO. We interpret these results to mean that dihydroprenyl phosphates with more than seven isoprene units have apoptosis-inducing activity and that their signal is mediated by caspase-3-like activation.

Apoptosis↗
PubMed1998

Myocardial fatty acid metabolism in diabetic mice with 125I-BMIPP.

In patients with diabetes mellitus, the existence of diabetic cardiomyopathy was substantiated. This study was undertaken to evaluate the myocardiac fatty acid metabolism of diabetic mice (n = 21) and controls (n = 21) in 125I-BMIPP in fasted and unfasted states. 125I-BMIPP of 370 kBq was given and thirty minutes later, animals from both groups were killed. Samples of hearts, liver and other organs were removed, weighed and then counted in a scintillation counter. The percent injected dose/g of hearts of diabetic mice was significantly reduced compared to controls in unfasted (p < 0.05) and fasted (p < 0.01) groups. These findings may reflect impaired fatty acid utilization of the hearts in diabetic mice compared to controls.

Animals↗