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Biomedical subjects

M Oshima

Publications and source records attributed to M Oshima.

At least 145 records · Page 8Linked to original sources

Induction of the fundic mucosa-specific glycolipid with dimethylformamide in gastric-cancer cell lines.

We have previously reported that a glycolipid GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer named NGM-1 is present specifically in the human gastric fundic mucosa, but not in other organs. In gastric-cancer tissue and cancer cell lines, this glycolipid completely disappears. These findings imply that NGM-1 is expressed only in well-differentiated fundic mucosa. The purpose of this study is to examine the expression of NGM-1 as a differentiation-related molecule. A gastric cell line AZ521 was cultured in the medium with various reagents which had been reported to induce differentiation in cancer cells. The growth of AZ521 was suppressed by the addition of 0.8% dimethylformamide (DMF) to the medium, but not by addition of dimethylsulfoxide (DMSO), retinoic acid or butyric acid. In the ganglioside fraction of the cells cultured with DMF, a glycolipid regarded as NGM-1 which had not been present before treatment was detected using a monoclonal antibody. Suppression of the proliferation of AZ521 by eliminating the serum from the medium could not induce the expression of NGM-1. A colonic cell line treated with DMF also failed to express the glycolipid. The synthase activity of NGM-1 was elevated in the AZ521 cells treated with DMF, but not with DMSO. These results demonstrate that the expression of NGM-1 is induced by DMF specifically in gastric-cancer cells, and suggest the possibility that NGM-1 is a differentiation-related molecule.

Butyrates↗

Suppression of experimental autoimmune myasthenia gravis by epitope-specific neonatal tolerance to synthetic region alpha 146-162 of acetylcholine receptor.

A gene conversion event between Ebb and Abb in the B6.C-H-2bm12 (bm12) strain, which alters three amino acids in the C-terminal half of the first domain of Abb (Ile-67-->Phe; Arg-70-->Gln; Thr-71-->Lys) resulted in resistance to experimental autoimmune myasthenia gravis (EAMG) pathogenesis. To study the effect of bm12 mutation on the T-cell responses to epitopes of acetylcholine receptor (AChR)-alpha subunit, C57BL6 (B6) and bm12 mice were primed with Torpedo californica AChR, and the profiles of T-lymphocyte proliferation were determined with 18 synthetic overlapping peptides encompassing the entire extracellular portion of the AChR-alpha subunit. The proliferative responses of AChR-primed bm12 lymphocytes were markedly reduced to two (alpha 146-162 and alpha 182-198) of the three AChR peptides (alpha 111-126, alpha 146-162, and alpha 182-198) that are immunodominant in B6 mice. Thus, the Ab residues encompassing the region 67-71 determine the immunogenicity of two of the AChR-alpha subunit T-cell epitopes. To test the involvement of AChR-alpha chain epitopes within peptide alpha 146-162 in EAMG pathogenesis, B6 mice were neonatally tolerized with soluble peptide alpha 146-162, and subsequently immunized with AChR in complete Freund's adjuvant. Neonatal tolerance to AChR or to peptide alpha 146-162 reduced the incidence of clinical myasthenia gravis and suppressed serum anti-AChR antibodies. This indicates the involvement of T-cell epitopes within AChR-alpha subunit region alpha 146-162 in EAMG pathogenesis. Neonatal tolerance to peptide alpha 146-162 could have caused specific clonal deletion, and/or clonal anergy, and/or recruited suppressor cells to prevent clinical EAMG. Presumably, epitope(s) with AChR alpha 146-162, in the context of Ab encompassing region 67-71, stimulate specific T helper cells which interact with specific B cells to produce pathogenic antibodies, the primary culprit causing the end plate lesion in patients with myasthenia gravis.

Amino Acid Sequence↗

Amino acid substitutions outside a preselected antigenic region in hemoglobin affect the binding to monoclonal antibodies obtained by immunization with the synthetic region.

It is often assumed that amino acid substitutions outside a protein antigenic site have no effect on the reactivity of a protein variant with antibodies, especially monoclonal antibodies (mAbs). Substitutions that exert an effect on the reactivity of a protein variant with mAbs are frequently considered to be within the antigenic site of the mAb. To test this assumption, two mAbs [IgG1(k) and IgG2a(k)] were prepared by immunization with a synthetic peptide corresponding to region 63-78 of the alpha chain of human hemoglobin (Hb). The peptide was used as an immunogen in its free form (i.e., without conjugation to a carrier), so that the results will not be made ambiguous by peptide modification nor by an immune response to sites spanning peptide and protein carrier. In addition to their reaction with human Hb, the mAbs were also studied with four primate Hbs which had no substitutions within region alpha 63-78 and only a limited number of substitutions which occurred outside of, and at considerable distances in three-dimensional (3D) structure from, this region. Inhibition studies revealed substantial differences in the binding affinities of some of the primate Hbs, relative to human Hb. Some of the substitutions caused major decreases in binding, although they were at considerable distances in the 3D structure from the indicated site residues. It is concluded that substitutions in a protein, even when distant from an antigenic site, can exert major influences on the protein's reactivity with anti-site mAbs.

Amino Acid Sequence↗

Recurrent malignant glioma: detection with 131I labeled monoclonal antibody G-22, positron emission tomography and magnetic resonance imaging.

A 45-year-old man with suspected recurrent malignant glioma was evaluated by magnetic resonance imaging (MRI), positron emission tomography (PET) and 131I labeled monoclonal antibody G-22 (G-22) scan. Following Gadolinium-DTPA, a TI-weighted spin echo image (TR 500 msec, TE 20 msec) demonstrated a large mass with an irregular margin in the left temporo-parietal area. An 18F labeled fluorodeoxyglucose PET study demonstrated marked accumulations in the left temporo-parietal area. Serial 131I-G-22 scintigraphy was obtained for a week after the injection. The uptake was most increased on the 2nd day after the injection. 131I G-22 was specific for tumor-associated antigens.

Glioma↗

Bile leakage after laparoscopic cholecystectomy demonstrated with 99mTc-PMT hepatobiliary scintigraphy.

A 41-year-old woman underwent laparoscopic cholecystectomy for the treatment of gallstone and adenomyomatosis. One month after laparoscopic cholecystectomy, hepatobiliary scintigraphy was performed with 99mTc-Sn-N-pyridoxyl-5-methyltryptophan (PMT) to evaluate the presence of a bile leak and/or other complication. A biliary extravasation was noted in the left upper quadrant within 60 minutes. At five hours post injection, a progressive accumulation of 99mTc-PMT was noted in the lesser sac, the right and left paracolic gutter and in the pouch of Douglas. A diagnosis of biliary leakage was made. The patient underwent exploratory laparotomy to repair the leak from the cystic duct stump.

Adult↗

Myocardial SPECT and left ventricular performance study using a single Tc-99m teboroxime injection. Comparison with thallium-201 myocardial SPECT.

Myocardial SPECT using teboroxime was compared to thallium SPECT in 26 patients undergoing cardiac catheterization. Agreement between thallium SPECT and teboroxime SPECT for the identification of myocardial segments was 209/235 (89%). A significant correlation was found in 15 patients between the left ventricular ejection fraction by teboroxime first-pass study and the ejection fraction by contrast ventriculography. In nine patients with myocardial infarction and/or multivessel coronary artery disease, the ejection fraction revealed a mean decrease from 0.52 at rest to 0.46 at exercise. Teboroxime makes it possible to perform an exercise first-pass study of left ventricular ejection fraction followed by myocardial perfusion imaging.

Adult↗

Acute effect of percutaneous transvenous mitral commissurotomy on ventilatory and hemodynamic responses to exercise. Pathophysiological basis for early symptomatic improvement.

BACKGROUND: Improvement of exertional dyspnea occurs immediately after percutaneous transvenous mitral commissurotomy (PTMC), but the pathophysiological basis for this early symptomatic improvement has not been elucidated. METHODS AND RESULTS: Exercise hemodynamic measurement and exercise ventilatory measurement with arterial blood gas analysis were performed in 21 patients aged 50.4 +/- 9.5 years (mean +/- SD) with symptomatic mitral stenosis before and a few days after PTMC. Exercise ventilatory measurement were also performed in 14 normal control subjects aged 48.9 +/- 4.9 years. After PTMC, mitral valve area increased (from 1.0 +/- 0.3 to 1.7 +/- 0.3 cm2, P < .001), mean mitral gradient (from 12.2 +/- 5.2 to 5.2 +/- 2.2 mm Hg, P < .001), and mean left atrial pressure (from 18.7 +/- 6.1 to 12.1 +/- 4.0 mm Hg, P < .001) decreased. All patients experienced significant symptomatic improvement soon after PTMC. Comparison of hemodynamic parameters at the same ergometer work rate showed a significant decrease in pulmonary artery systolic pressure (from 77 +/- 18 to 67 +/- 14 mm Hg, P < .001) and diastolic pressure (from 36 +/- 10 to 28 +/- 7 mm Hg, P < .001) and a significant increase in cardiac output (from 6.4 +/- 1.4 to 8.1 +/- 1.9 L/min, P < .001). Despite the improvement in exercise hemodynamics and symptoms, exercise capacity determined by peak oxygen uptake (from 18.0 +/- 2.9 to 18.6 +/- 3.1 mL.kg-1 x min-1) and anaerobic threshold (from 11.7 +/- 2.4 to 12.0 +/- 2.4 mL.kg-1 x min-1) remained unchanged. Excessive exercise ventilation, as assessed by the slope of the regression line between expired minute ventilation and carbon dioxide output, decreased significantly from 37.2 +/- 6.7 to 33.9 +/- 5.8 (P < .001), but remained significantly higher than that in the normal subjects (27.9 +/- 3.6, P < .01). The ratio of total dead space to tidal volume and total dead space per breath during exercise decreased significantly after PTMC (P < .05). The change in excessive exercise ventilation after PTMC was correlated with the change in dead space to tidal volume ratio (r = .59). CONCLUSIONS: Significant relief of exertional dyspnea immediately after PTMC is not accompanied by an improvement in exercise capacity. A decrease in excessive ventilation due to a decrease in physiological dead space resulting from hemodynamic improvement partly contributes to the early relief of symptoms after PTMC. However, lung compliance, which was not measured in the present study, may have changed after PTMC. This change may also contribute to the symptomatic improvement.

Anaerobic Threshold↗

[Evaluation of newborns with brain disease using 123I-IMP SPECT].

Eleven newborns with suspected cerebral disease were evaluated using 123I-IMP SPECT. In a normal subject, high uptake was shown in the sensorimotor cortex, thalamus, midbrain-brainstem, and cerebellar vermis. Decreased perfusion was also noted in the frontal lobe. In hypoxic ischemic encephalopathy (HIE), diffuse decreased uptake which showed no redistribution in the white matter was seen in two patients. These two patients had a poor prognosis. In one of the other 4 patients with HIE, persistent defect in parasagittal area was recognized and the patient also had a poor prognosis. In one of two patients with tuberous sclerosis, 123I-IMP SPECT showed high uptake in the area of increased density shown in CT. Thus, 123I-IMP SPECT of newborn has characteristic findings different from the adult. This tracer also might have a prognostic value of clinical improvement following HIE.

Amphetamines↗

Substrate specificity and distribution of UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase in the human stomach.

The detailed substrate specificity of the UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase to form the Sd(a+) blood group active carbohydrate determinant GalNAc beta 1-4(NeuAc alpha 2-3)Gal was studied using a membrane fraction prepared from human gastric fundic mucosa. Various sialosylated oligosaccharides and gangliosides were examined as acceptor substrates. Oligosaccharide substrates were fluorescence-labelled with 2-aminopyridine, and the transferase activity was quantified by h.p.l.c. using a reversed-phase column. The structures of the products were determined by glycosidase degradation and proton n.m.r. 3'-Sialyl-lactose (II3NeuAcLac), 3'-sialyl-lactotetraose (IV3NeuAcLc4), and 3'-sialyl-lactoneotetraose (IV3NeuAcnLc4) were good substrates for the beta 1-4GalNAc transferase in gastric fundic mucosa, but 6'-sialyl-lactoneotetraose (IV6NeuAcnLc4) or 6'-sialyl-lactose (II6NeuAcLac) were not. Gangliosides with a terminal NeuAc alpha 2-3Gal residue such as GM3, sialylparagloboside, GM1b and GD1a were also studied. The activity of beta 1-4GalNAc transfer to sialylparagloboside was much higher than that to GM2, GM1b or GD1a in spite of them having the same terminal residue. Measurement of the activity of the beta 1-4GalNAc transferase in biopsy specimens demonstrated that the activity was localized in gastric fundic mucosa and was absent in pyloric mucosa, intestinal metaplasia and gastric cancer tissue. Thus the beta 1-4GalNAc transferase present specifically in fundic mucosa required a NeuAc alpha 2-3Gal residue connected to either type-1-chain or type-2-chain oligosaccharides. In glycolipids, the acceptor specificity was restricted to NeuAc alpha 2-3Gal beta 1-4GlcNAc because the NeuAc alpha 2-3Gal beta 1-3GalNAc structure in ganglio-series glycolipids was not a good acceptor substrate.

Aminopyridines↗

Epitope-specific suppression of antibody response in experimental autoimmune myasthenia gravis by a monomethoxypolyethylene glycol conjugate of a myasthenogenic synthetic peptide.

A synthetic peptide corresponding to a myasthenogenic region of Torpedo californica acetylcholine (AcCho) receptor (AcChoR) alpha subunit, AcChoR alpha-(125-148), was conjugated to monomethoxypolyethylene glycol (mPEG). Injection of mice with the mPEG-AcChoR alpha-(125-148) conjugate and subsequent immunization with whole Torpedo AcChoR suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by electrophysiological criteria. In anti-AcChoR sera from these animals, the antibody response against unconjugated AcChoR alpha-(125-148) was decreased, while the antibody responses against whole AcChoR and other epitopes were not altered. There were no detectable changes in T-cell proliferation responses to AcChoR alpha-(125-148) or to whole AcChoR in these animals. Prior injections with a "nonsense" peptide-mPEG conjugate had no effect on responses to the subsequent immunization with whole Torpedo AcChoR. The results indicate that the mPEG-AcChoR alpha-(125-148) conjugate has epitope-specific tolerogenicity for antibody responses in EAMG and that the AcChoR alpha-subunit region comprising residues 125-148 plays an important pathophysiological role in EAMG. The epitope-directed tolerogenic conjugates may be useful for future immunotherapies of human myasthenia gravis. The strategy of specific suppression of the antibody response to a predetermined epitope by using a synthetic mPEG-peptide conjugate may prove useful in manipulation and suppression of unwanted immune responses such as autoimmunity and allergy.

Amino Acid Sequence↗

Comparison of thallium-201 and technetium-99m teboroxime myocardial single photon emission tomography with coronary arteriography.

Myocardial single photon emission tomography (SPET) using technetium-99m teboroxime (teboroxime) was studied and the results compared with those of thallium-201(thallium) SPET and coronary arteriography in 19 patients. Resting teboroxime SPET was performed initially. Two hours later, exercise teboroxime SPET was performed. Exercise ergometer tests for both teboroxime and thallium were carried out in a supine position. The levels of exercise achieved for both tests were similar. Agreement for the identification of myocardial segments between thallium SPET and teboroxime SPET was 147/171(86%) (NS). When a significant stenosis was defined as greater than or equal to 75% or greater than or equal to 50%, agreement between two radiopharmaceuticals for the detection of diseased vessels was 89% (NS, k = 0.601) or 88% (NS, k = 0.713), respectively. In only 2/19 cases were inferior and posterior segments (3/171) difficult to interpret in teboroxime SPET due to hepatic activity. Thus, teboroxime SPET with a short data acquisition time resulted in a rapid completion for each study and had a good correlation with thallium SPET.

Adult↗

Initial stage of Legg-Calve-Perthes disease: comparison of three-phase bone scintigraphy and SPECT with MR imaging.

Twenty-one patients with initial stage Legg-Calve-Perthes (LCP) disease were examined by three-phase bone scintigraphy, single photon emission scintigraphy (SPECT), and magnetic resonance (MR) imaging. On dynamic study, increased activity was present in the epiphysis or the growth plate in 39%; the corresponding figure for blood-pool images was 94%. Pinhole images demonstrated the lateral stripe of revascularization in 57% of patients. Decreased signal intensity in the epiphysis on T1-weighted images proved to be the most sensitive indicator of epiphyseal necrosis on MR imaging and was absent in only 10% of the cases. The subchondral fracture occurred in 62% (including the above 10% of cases), identified by T1-weighted image. Cartilaginous hypertrophy, detected by T1-weighted image, had a high incidence (81%). Joint effusion was identified on T2-weighted images in 90% of patients. The cross-sectional views provided by SPECT and MR imaging permits a better appreciation of the extent of epiphyseal necrosis in LCP disease.

Bone and Bones↗

Comparison of Tc-99m HMPAO fast SPECT with Tc-99m HMPAO conventional SPECT in patients with acute stroke.

Tc-99m HMPAO SPECT is more likely to detect a stroke in early stages than CT. However, a conventional HMPAO SPECT study takes at least 30 minutes to complete. This paper compares fast Tc-99m HMPAO SPECT scans and conventional Tc-99m HMPAO SPECT scans with respect to spatial resolution and diagnostic efficacy in vitro and in a small series of patients, respectively. The spatial resolution of fast Tc-99m HMPAO SPECT did not match that of images obtained from conventional SPECT, though the difference proved to be of no clinical significance. Since fast SPECT requires only one-fourth to one-fifth the time necessary for conventional SPECT, it may be more suitable for investigating cases of acute stroke in critical clinical situations.

Acute Disease↗