Search PubMed⌕ Search

Biomedical subjects

A Abe

Publications and source records attributed to A Abe.

At least 145 records · Page 8Linked to original sources

Induction of humoral and cellular anti-idiotypic immunity by intradermal injection of naked DNA encoding a human variable region gene sequence of an immunoglobulin heavy chain in a B cell malignancy.

The idiotypic determinants of a B cell neoplasia could provide a tumor-specific target for vaccinating patients against their B cell tumors. Several approaches for inducing idiotype-specific immunization have been reported, but their major theoretical focus was related to the induction of humoral immunity. We have investigated an immunization procedure with naked DNA encoding human variable region gene sequences of an immunoglobulin heavy chain (VH), which may generate both humoral and cellular immune responses against the idiotype of a B cell acute lymphoblastic leukemia (ALL). Using polymerase chain reaction (PCR) amplification, we investigated heavy chain variable region genes obtained from an ALL patient and whether they could induce humoral and cellular immune responses in DBA/2 mice. The VH sequence was cloned into a mammalian expression vector for intradermal DNA vaccination and into a bacterial expression vector to obtain VH protein for Western blotting. The mammalian expression vector encoding the VH gene was injected into mice three times at 7-day intervals and was transduced into P1HTR which is a syngeneic tumor of DBA/2, to serve as target cells to detect cellular immunity. Spleen cells from the inoculated mice exhibited a significant cytotoxic T lymphocyte response to the target cells. By Western blotting, we could also detect trace levels of anti-VH antibodies in all mice serum. This approach for the induction of cellular immunity by intradermal injection is easy and variable region-specific, and may be used as vaccines after chemotherapy treatment of B cell malignancies.

Amino Acid Sequence↗

[The role of the interaction between macrophages and mesangial cells in the progression of IgA nephropathy].

IgA nephropathy is the most common form of glomerulonephritis in the world. Approximately, 20 to 30% of IgA nephropathy patients progress to end stage renal failure in 20 years. However, the mechanism (s) underlying the progression of IgA nephropathy has not been fully understood. The purpose of this study was to elucidate the role of the interaction between macrophages and mesangial cells in the progression of IgA nephropathy. Renal biopsy specimens from 40 patients with IgA nephropathy were examined to investigate the relationship between glomerular infiltration of monocytes/macrophages (Mo/M phi), glomerular expression of monocyte-specific chemoattractant, and their clinicopathological findings. The results led to the following conclusions. 1. The localization of Mo/M phi within the glomerulus was identified as intracapillary or intramesangial by immuno-cytochemistry with monoclonal antibody against CD68. 2. Close relationships between mesangial expressions of M-CSF and MCP-1, and mesangial localization of Mo/M phi strongly suggested that mesangial production of these factors, in concert with glomerular ICAM-1 expression, enhances the recruitment and survival of Mo/M phi in the mesangium. 3. It was suggested that Mo/M phi localized in the mesangium play an important role in the progression of IgAN through increasing the production of matrix by mesangial cells.

Adolescent↗

[Continuous ambulatory peritoneal dialysis ameliorated metabolic disturbances of a patient with chronic renal failure caused by glycogen storage disease type I].

A 30-year-old woman with chronic renal failure (CRF) due to glycogen storage disease Type I (GSD I) was admitted for dialysis. Hemodialysis (HD) was introduced as the primary therapeutic modality. However, maintenance HD was very difficult to conduct because of hypotension during the HD sessions. Furthermore, hypoglycemia and metabolic disturbances persisted. After changing from HD to CAPD, fasting blood sugar was significantly elevated through a continuous glucose supply from the dialysate. The values of ketone, non-esterified fatty acid, blood urea nitrogen/creatinine (BUN/ Cr), and glucagon were improved. CAPD not only controlled uremia, but also ameliorated the metabolic disturbances of GSD I. Therefore, we conclude that CAPD is superior to HD as a dialytic modality for patients with CRF due to GSD I.

Adult↗

Ceramide formation during heat shock: a potential mediator of alpha B-crystallin transcription.

Ceramide has been identified as a potential second messenger that may mediate cell differentiation and apoptosis after exposure to hormonal agonists such as 1 alpha, 25-dihydroxyvitamin D3, tumor necrosis factor alpha, or gamma-interferon. The secondary cellular events that follow ceramide generation remain undefined. We report that in NIH WT-3T3 cells, ceramide induces an enhancement of gene transcription of alpha B-crystallin, a small heat shock protein. The levels of alpha B-crystallin, as measured by Northern blot and immunoblot analyses, were increased by the addition of an exogenous short-chain ceramide, N-acetylsphingosine, or by increasing endogenous intracellular ceramide by inhibition of glucosylceramide synthase. Similar effects were not seen in the expression of the closely related gene, Hsp25. To ascertain whether ceramide-mediated gene transcription was a feature of the heat shock response, cell ceramide was measured in heat shocked cells and observed to be elevated 2-fold immediately upon the return of cells to 37 degrees C. Thus ceramide formed after heat shock treatment of 3T3 cells may mediate the transcription events associated with the cell stress response.

3T3 Cells↗

Properties of the omega-hydroxylation system of docosahexaenoic or arachidonic acid in brain or liver homogenate of rat.

The homogenate of a brain or liver obtained from a 1-55-day-old rat was incubated with NADPH and docosahexaenoic or arachidonic acid as the substrate. omega-Hydroxydocosahexaenoic or omega-hydroxyeicosatetraenoic acid from an incubation mixture of the homogenate was detected on a selected-ion monitoring chromatogram of reversed phase-HPLC-thermospray-mass spectrometry. omega-Hydroxylation activity in the brain homogenate considerably increased with growth up to 55 days. Activity in the liver homogenate decreased much with growth up to 55 days. omega-Hydroxylation activity in homogenates of rat brain gray matter, white matter, medula oblongata and cerebellum was much the same. omega-Hydroxylation activity of docosahexaenoic acid in rat brain homogenate was maximal at pH 7.5-8.0 in 50 mM Tris-HCl buffer and was inhibited by CO gas, metyrapone, ADP-Fe3+, heat treatment at 100 degrees C for 5 min and without NADPH. Based on these results, it is suggested that omega-hydroxylation activity is associated with cytochrome P-450 without NADPH-ADP-Fe(3+)-dependent lipid peroxidation, and the omega-hydroxylation system may be a metabolic pathway of the fatty acids in adult rat brain or neonatal rat liver. Since omega-hydroxyeicosatetraenoic acid produces relaxation of artery, it is suggested that blood flow changes in rat brain or liver with growth are caused by omega-hydroxylation activity changes in these organs with growth.

Animals↗

Spatial orientation of the reentrant circuit of idiopathic left ventricular tachycardia.

In 6 patients with idiopathic left ventricular VT, the spatial orientation of the reentrant circuit was estimated from the results of transient entrainment of VT with rapid pacing at different sites. The entrance to the area of slow conduction was located toward the outflow tract, whereas the exist was located at the apicoposterior area of the left interventricular septum.

Adult↗

Transcriptional regulation and promoter sequence of the spvR gene of virulence plasmid pKDSC50 in Salmonella choleraesuis serovar Choleraesuis.

The transcript of the spvR gene on the virulence plasmid, pKDSC50, of Salmonella choleraesuis serovar Choleraesuis was detected for the first time by Northern blot analysis, and the transcriptional regulation of the spvR gene was investigated. The transcription of the spvR was negatively regulated by spvA and spvB, and enhanced at stationary phase under control of a sigma factor RpoS (sigma 38). The spvR transcript was 2.4 kilonucleotides in Salmonella cells, and deduced to encode SpvR and SpvA, suggesting that SpvA but not SpvB is the functioning repressor in spv operon. The promoter sequence analysis revealed that spvR was transcribed from a single promoter and the 5' end of the transcript was located at 18 bp upstream from the start codon of spvR. Sequential similarity between the promoter of spvR and other sigma 38-controlled genes was not found, but the consensus sequence was found in -10 to -35 region of spvR and spvA, which may correlate to our previous data indicating that both genes were positively regulated by the SpvR protein.

Bacterial Proteins↗

omega-Hydroxylation of docosahexaenoic acid or arachidonic acid in human colonic well differentiated adenocarcinoma homogenate.

Human colonic well differentiated adenocarcinoma homogenate was incubated with NADPH and docosahexaenoic acid (22:6(n-3)) or arachidonic acid (20:4(n-6)) as a substrate. On a selected ion monitoring chromatogram obtained with reversed phase-high-performance liquid chromatography thermospray mass spectrometry, omega-hydroxydocosahexaenoic acid (omega-HDHE) or omega-hydroxyeicosatetraenoic acid (omega-HETE) from an incubation mixture of the homogenate was detected in significant amount, compared to that from a colonic region remote from the carcinoma. In contrast, epoxydocosapentaenoic acids and the dihydroxy derivatives from 22:6(n-3) or epoxyeicosatrienoic acids and the dihydroxy derivatives from 20:4(n-6) were detected in low amounts, compared to that from a colonic region remote from the carcinoma. The results suggest that highly active NADPH-dependent omega-oxidations of polyunsaturated fatty acids occur in colonic adenocarcinoma homogenate.

Adenocarcinoma↗

DNA sequencing of the gene encoding a bacterial superantigen, Yersinia pseudotuberculosis-derived mitogen (YPM), and characterization of the gene product, cloned YPM.

Previously, we found a novel bacterial superantigen from Yersinia pseudotuberculosis, designated Y. pseudotuberculosis-derived mitogen (YPM). In the present study, we analyzed the DNA sequence of the gene encoding YPM. The YPM gene was cloned into a plasmid vector pMW119 and expressed in Escherichia coli DH10B. Like the native YPM, the cloned YPM required the expression of MHC class II molecules on accessory cells in the induction of IL-2 production by human T cells. TCR-V beta repertoire of human T cells reactive with the cloned YPM was V beta 3, V beta 9, V beta 13.1, and V beta 13.2. This repertoire is the same as that of T cells reactive with the native YPM. These results indicate that the cloned YPM expressed in E. coli is identical to the native YPM. Sequencing of the YPM gene revealed that the gene contained an open reading frame of 456 base pairs encoding a precursor form of 151 amino acid residues with m.w. 16,679 that is processed into a mature form of 131 amino acid residues with m.w. 14,529. Homology analysis revealed that the homology of amino acid sequence is quite low among YPM and other well known bacterial superantigens. We designated the gene encoding YPM as ypm.

Amino Acid Sequence↗

High-performance liquid chromatography-thermospray mass spectrometry of omega-carboxyleukotriene B4 and omega-hydroxyleukotriene B4 from an incubation mixture of human colonic well-differentiated adenocarcinoma homogenate.

A method for the analysis of omega-carboxyleukotriene B4 and omega-hydroxyleukotriene B4 in human colonic carcinoma homogenate is described. The hydroxy groups of the leukotriene metabolite were acetylated by acetic anhydride, and the mixture was partially purified on a Sep-Pak C18 cartridge and analysed by reversed-phase HPLC-thermospray MS. Generally, the base ion, [MH-2(60)]+, is produced through elimination of two acetic acid (60 mass units) molecules from the protonated molecular ion. On selected-ion monitoring, standard curves for omega-carboxy- or omega-hydroxyleukotriene B4 showed a linear relationship over the range 72-1500 pmol. The assay based on selected-ion monitoring was applied to an extract from human colonic carcinoma homogenate. When a homogenate of human colonic well-differentiated adenocarcinoma was incubated with NADPH and leukotriene B4 (60.6 nmol) as a substrate, the conversion of precursor leukotriene B4 to omega-carboxyleukotriene B4 or omega-hydroxyleukotriene B4 was 0.33 or 3.17%, respectively. Based on these results, it is suggested that carcinoma cells themselves or leukocytes at the hostsite in a region of human colonic well-differentiated adenocarcinoma are performing omega-oxidation through NADPH-dependent omega-hydroxylation of leukotriene B4.

Adenocarcinoma↗

Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases.

In an attempt to define the basis for sphingolipid regulation of cell proliferation, we studied the effects of glucosylceramide (GlcCer) synthase inhibition by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on NIH 3T3 cells overexpressing insulin-like growth factor-1 (IGF-1) receptor. PDMP treatment resulted in a time-dependent decrease in GlcCer levels and an increase in cellular ceramide levels. PDMP abolished serum and IGF-1-stimulated cell proliferation, as measured by a reduction in [3H]thymidine incorporation, protein, and DNA levels. However it did not affect IGF-1-mediated early signaling events, including receptor tyrosine kinase, MAP kinase, and phosphatidylinositol 3-kinase activities. Two-color flow cytometry with propidium iodide and 5-bromo-2'-deoxyuridine monophosphate labeling revealed an arrest of the cell cycle at G1/S and G2/M transitions in an asynchronous population of cells. These changes were time dependent, with maximal effects seen by 12-24 h. Removal of PDMP from the cell medium resulted in reversal of the cell cycle changes, with cells re-entering the S phase. The cell cycle arrest at the G1/S and G2/M transitions was confirmed in cells synchronized by pretreatment with nocodazole, aphidicolin, or hydroxyurea, and released from blockade in the presence of PDMP. A decrease in the activities of two cyclin-dependent kinases, p34cdc2 kinase and cdk2 kinase, was observed with PDMP treatment. When cell ceramide levels were increased by N-acetylsphingosine, comparable changes in the cell cycle distribution were seen. However, sphingomyelinase treatment was without effect. Therefore, it appears that ceramide mediates in part the inhibitory effect of GlcCer synthase inhibition on IGF-1-induced cell proliferation in 3T3 cells. The rapid production of decreased cyclin-dependent kinase activities by PDMP suggests that one of the crucial sites of action of the inhibitor lies in this area.

3T3 Cells↗

Acute myeloblastic leukemia (M2) with translocation (7;11) followed by marked eosinophilia and additional abnormalities of chromosome 5.

We present an 18-year-old woman who was diagnosed with acute myeloblastic leukemia (AML M2), and in whom chromosome analysis of bone marrow cells revealed t(7;11), an abnormality rarely found in leukemias with a differentiation potency. She relapsed 1 year after complete remission was achieved by chemotherapy. Bone marrow examination then revealed a t(7;11) abnormality in 48 of 50 metaphases examined, even when there were less than 7.5% leukemic blasts in the marrow, indicating that the morphologically normal cells were derived from leukemic blasts. The number of leukemia clones with the additional abnormalities in chromosome 5 increased, with concurrent development of eosinophilia, fever, asthma-like symptoms, erythema, itching, and hepatosplenomegaly. Elevation of interleukin 5 (IL-5) in serum and an enhanced expression of IL-5 mRNA were also detected. The increase in IL-5 may have been produced by an abnormality on chromosome 5.

Adolescent↗

Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition.

Glucocorticoids are important regulators of renal phosphate transport. This study investigates the role of alterations in renal brush border membrane (BBM) sodium gradient-dependent phosphate transport (Na-Pi cotransporter) mRNA and protein abundance in the dexamethasone induced inhibition of Na-Pi cotransport in the rat. Dexamethasone administration for 4 d caused a 1.5-fold increase in the Vmax of Na-Pi cotransport (1785 +/- 119 vs. 2759 +/- 375 pmol/5 s per mg BBM protein in control, P < 0.01), which was paralleled by a 2.5-fold decrease in the abundance of Na-Pi mRNA and Na-Pi protein. There was also a 1.7-fold increase in BBM glucosylceramide content (528 +/- 63 vs. 312 +/- 41 ng/mg BBM protein in control, P < 0.02). To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol (PDMP). The resultant 1.5-fold decrease in BBM glucosylceramide content (199 +/- 19 vs. 312 +/- 41 ng/mg BBM protein in control, P < 0.02) was associated with a 1.4-fold increase in Na-Pi cotransport activity (1422 +/- 73 vs. 1048 +/- 85 pmol/5 s per mg BBM protein in control, P < 0.01), and a 1.5-fold increase in BBM Na-Pi protein abundance. Thus, dexamethasone-induced inhibition of Na-Pi cotransport is associated with a decrease in BBM Na-Pi cotransporter abundance, and an increase in glucosylceramide. Since primary alteration in BBM glucosylceramide content per se directly and selectively modulates BBM Na-Pi cotransport activity and Na-Pi protein abundance, we propose that the increase in BBM glucosylceramide content plays an important role in mediating the inhibitory effect of dexamethasone on Na-Pi cotransport activity.

Animals↗

Assessment of malocclusion of Japanese junior high school pupils aged 12-13 years in Iwate prefecture according to the Dental Aesthetic Index (DAI).

The purpose of this investigation is to grasp the actual condition of malocclusion in Japanese junior high school pupils using the Dental Aesthetic Index (DAI). A total of 218 junior high school pupils aged 12-13 years were examined according to DAI. About 40% of the subjects had incisal crowding. The percentage of subjects with incisal spacing was 24%, and 71% of them had diastema of 1 mm or more. The percentage of subjects with anterior irregularity on the upper and lower arch was 39% and 33%, respectively. The percentage of subjects with anterior maxillary overjet and mandibular protrusion of 1 mm or more was 85% and 6% respectively. Dislocation by more than a half-cusp in the proximal or distal relationship in the molars was observed in 26% of all subjects. Mean +/- SD of DAI score was 25.3 +/- 7.3.

Adolescent↗