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T Ariga

Publications and source records attributed to T Ariga.

At least 163 records · Page 9Linked to original sources
PubMed1989

Accumulation of glycosphingolipids in spinal and sympathetic ganglia of a symptomatic heterozygote of Fabry's disease.

Fabry's disease is an X-linked disorder of glycolipid catabolism. We have found a symptomatic heterozygous female with cardiomyopathy and severe pain in the extremities. We studied histochemically and biochemically the accumulated glycolipids in spinal and sympathetic ganglia of the patient. Histochemical examination demonstrated the marked glycolipid deposits that have been observed in heterozygous males in these ganglia. Gas-liquid chromatography (GLC) revealed that these accumulated glycolipids were characterized as globotriaosylceramide (Gb3cer) and galabiosylceramide (Ga2cer). In the heterozygous female, the accumulations of Gb3cer in spinal and sympathetic ganglia were, respectively, 34 and 48 times the amount in normal controls. This is the first report on quantitative and qualitative analyses of the accumulated glycolipids in spinal and sympathetic ganglia of a heterozygous carrier female.

Fabry Disease↗
PubMed1989

Type I C1 inhibitor deficiency with a small messenger RNA resulting from deletion of one exon.

The molecular genetic basis of C1 inhibitor (C1 INH) deficiency in a patient with type I hereditary angioneurotic edema was studied. This patient was found to have an abnormally short C1 INH mRNA together with a normal message. Restriction fragment length polymorphism of the C1 INH gene was detected by Southern blot analysis of the patient's DNA after digestion with Pst I or Sac I, and hybridization with a full-length C1 INH cDNA. Hybridization of the same blot with three different fragments of the full-length cDNA suggested that exon VII and portions of both flanking introns were deleted in the C1 INH gene. Northern blot analysis of RNA from cultured monocytes, using a probe corresponding to exon VII, also indicated that the abnormal C1 INH mRNA had a deletion of these nucleotides. To confirm the hypothesis that the short C1 INH mRNA contained a deletion, the involved segment of the patient's C1 INH mRNA was amplified using the polymerase chain reaction (PCR). PCR amplification yielded two C1 INH DNA fragments of different lengths (380 and 160 bp). Southern blot and sequence analysis of both DNA fragments clearly revealed that the smaller 160-bp DNA was derived from the abnormal message and had a deletion of nucleotides corresponding to exon VII.

Angioedema↗
PubMed1988

Accumulation of a globo-series glycolipid having Gal alpha 1-3Gal in PC12h pheochromocytoma cells.

In a previous paper, we reported the presence of globoside as a major neutral glycolipid in PC12 pheochromocytoma cells [Ariga, T., Macala, L. J., Saito, M., Margolis, R. K., Greene, L. A., Margolis, R. U., & Yu, R. K. (1988) Biochemistry 27, 52-58]. Recently, we found that subcloned PC12h cells accumulated another unusual neutral glycolipid. In order to characterize this glycolipid, PC12h cells were subcutaneously transplanted into rats. The induced tumor tissue accumulated two major neutral glycolipids, which were purified by Iatrobeads column and preparative thin-layer chromatographies. One of the glycolipids was found to be globoside, and the other had a globotriaosyl structure with an additional terminal Gal alpha 1-3 residue. Its structure was determined by fast atom bombardment mass spectrometry, two-dimensional proton nuclear magnetic resonance spectrometry (2D NMR), permethylation study, sequential degradation with exoglycosidase, and mild acid hydrolysis to be Gal(alpha 1-3)Gal(alpha 1-4)Gal(beta 1-4)Glc(beta 1-1')Cer.

Adrenal Gland Neoplasms↗
PubMed1988

Changes in glycosphingolipids accompanying the differentiation of human squamous SQCC/Y1 cells.

SqCC/Y1 cells grow as a monolayer in culture and differentiate when maintained in the plateau phase; in the absence of serum these cells differentiate more rapidly. The differentiation is characterized by the stratification of the culture to form a structure consisting of several cellular layers, synthesis of specific keratins, and the attainment of the capacity to form a cornified cell membrane. The stratification process is indicative of the importance of cell-cell interactions during maturation. To study the relationship between membrane glycosphingolipids (GSLs) and the state of differentiation of SqCC/Y1 cells, GSLs were measured in cultures grown in the presence or absence of fetal calf serum. Glycolipids were isolated by diethylaminoethyl-Sephadex and Iatrobeads column chromatographies, and their distributions were determined by high-performance thin-layer chromatography. GM3 was the major ganglioside present in these cells. Other ganglioside components were tentatively identified as GM2, GM1, and GD3. Differences in ganglioside patterns were observed in differentiated cultures; the major changes were accumulation of GD3 and depletion of GM1. The predominant neutral GSLs in SqCC/Y1 cells were identified as Glc beta 1-1Cer, Gal beta 1-4Glc beta 1-1Cer, Gal beta 1-4Gal alpha 1-4Glc beta 1-1Cer, Gal NAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer, and three unknown complex GSLs. Differentiated cultures, however, showed variations in banding patterns, which include an increase in Glc beta 1-1Cer and Gal beta 1-4Glc beta 1-1Cer and a decrease in Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer and Gal NAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta-1Cer. These changes, however, were not observed when the cells were grown in the presence of epidermal growth factor or retinoic acid, factors which inhibit the differentiation process. The findings demonstrate significant changes in glycolipid composition of differentiated SqCC/Y1 cells grown in the absence of serum, suggesting that these lipids may be important to the differentiated state.

Carcinoma, Squamous Cell↗
PubMed1988

Lipid composition of PC12 pheochromocytoma cells: characterization of globoside as a major neutral glycolipid.

We have studied the lipid composition of PC12 pheochromocytoma cells cultured in the presence and absence of nerve growth factor (NGF). Neutral and acidic lipid fractions were isolated by column chromatography on DEAE-Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC). The total lipid concentration was approximately 220 micrograms/mg of protein, and the concentration of neutral glycolipids was 1.6-1.8 microgram/mg of protein for both NGF-treated and untreated cells. The neutral glycolipid fraction contained a major component, which accounted for approximately 80% of the total and which was characterized as globoside on the basis of HPTLC mobility, carbohydrate analysis, fast atom bombardment mass spectrometry, and mild acid hydrolysis. The major fatty acids of globoside were C16:0 (10%), C18:0 (16%), C22:0 (23%), C24:1 (17%), and C24:0 (24%). C18 sphingenine accounted for almost all of the long-chain bases. The other neutral glycolipids were tentatively identified as glucosylceramide (15%), lactosylceramide (4%), and globotriosylceramide (4.5%). The concentration of ganglioside sialic acid was approximately 0.34 and 0.18 microgram/mg of protein for cells grown in the presence and absence of NGF, respectively. Although there was an increase in ganglioside concentration in NGF-treated cells, NGF did not produce any differential effects on the relative proportions of the individual gangliosides. Several of the gangliosides appear to contain fucose, and one of these was tentatively identified as fucosyl-GM1. Brain-type gangliosides of the ganglio series were also detected by an HPTLC-immunostaining method. However, the fatty acid and long chain base compositions of PC12 cell gangliosides (and their TLC mobility) differ from those of brain gangliosides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1988

Preparation and characterization of antibodies against a sulfated glucuronic acid-containing glycosphingolipid.

In some patients with demyelinating neuropathy there are immunoglobulin M paraproteins that react with carbohydrate determinants shared by myelin-associated glycoprotein (MAG) and two peripheral nerve acidic glycolipids, termed sulfoglucuronosylglycosphingolipids (SGGLs). To study the antigenicity of these glycolipids, we immunized three New Zealand white rabbits with sulfoglucuronosylparagloboside (SGPG), a major SGGL in peripheral nerve, emulsified in Freund's complete adjuvant and keyhole limpet hemocyanin. All three rabbits inoculated with SGPG showed weight loss and mild weakness, predominantly in their hind feet, 2-5 weeks postinoculation (PI). Two of the three rabbits again showed moderate weakness 3 and 8 months PI, respectively. Electrophysiological studies demonstrated a slowed nerve conduction velocity in the sciatic nerve. Anti-SGPG antibody titers in sera were detected at dilutions of 1:1,000 to 1:2,500 by an enzyme-linked immunosorbent assay. Although all three rabbit sera reacted with SGGLs, two reacted with a desulfated form of SGPG and the other did not, suggesting a fine heterogeneity in antigenic specificity. As with sera from patients with demyelinative paraproteinemia, all rabbit sera reacted with MAG in human CNS and PNS myelin. They also reacted with MAG from bovine CNS myelin as well as several low-molecular-weight glycoproteins in bovine peripheral nerve myelin. Thus, we demonstrated that the rabbit antisera generated against SGPG have the same or similar antigenic specificity as those of the anti-MAG M-proteins from patients with neuropathy. The results suggest that an autoimmune response against the sulfoglucuronosyl residue may participate in the immunopathogenesis of this type of neuropathy.

Animals↗
PubMed1988

Induction of the CD4-8+ suppressor phenotype in CD4+8+ human thymocytes by phorbol myristate acetate.

Human thymocytes were separated according to differential agglutination by peanut lectin (PNA). In the fractions obtained, the distribution and quantitative expression of CD antigens was determined by two-color fluorescence flow cytometry. A major population of CD4+8+ and minor populations of CD4+8- and CD4-8+ cells existed in unfractionated thymocytes. Agglutination of human thymocytes by PNA led to a highly effective enrichment of the CD4+8+ phenotype in the PNA+ thymocytes, and left three distinct phenotypes, CD4+8+, CD4+8-, and CD4-8+, in the PNA-thymocytes. After treatment of the CD4+8+ cells in both PNA+ and PNA- fractions for 20 hr with phorbol 12-myristate 13-acetate (PMA), 60%-90% of the cells expressed the CD4-8+ phenotype, whereas the CD4+8+ phenotype was decreased to 1%-3% of the population. In addition, pretreatment of both PNA+ and PNA- thymocytes with PMA induced suppressor activity in these cells, as shown by inhibition of immunoglobulin secretion by pokeweed mitogen (PWM)-stimulated peripheral blood lymphocytes (PBL).

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Characterization of tumor-associated fucogangliosides from PC 12 pheochromocytoma cells.

PC 12h pheochromocytoma cells were subcutaneously transplanted into rat. We found the transplanted tumors accumulated some fucogangliosides associated with PC 12 cells. These gangliosides were isolated and purified by DEAE-Sephadex A-25 and Iatrobeads column chromatographies. Their structures were determined by fast atom bombardment mass spectrometry, proton nuclear magnetic resonance spectrometry, permethylation study, and sequential degradation using various exoglycosidases and mild acid hydrolysis. Two tumor-associated fucogangliosides were found to possess the blood group B determinant as follows: G6: IV2Fuc alpha, IV3Gal alpha, II3NeuAc, GgOse4Cer; G11: IV2Fuc alpha, IV3Gal alpha, II3 (NeuAc)2, GgOse4Cer. A ganglioside with the similar structure as ganglioside G6 was isolated from rat hepatoma cells (Holmes, E.H., and Hakomori, S-I. (1982) J. Biol. Chem. 257, 7698-7703). However, ganglioside G11 has not previously been reported in the literature. These fucogangliosides reacted with the monoclonal antibody prepared by immunizing mice with PC 12h cells. Other fucogangliosides were also found to accumulate in the transplanted tumor tissues. They were identified as fucosyl-GM1 and fucosyl-GDlb. These fucogangliosides did not react with the monoclonal antibody against PC 12h cells.

Adrenal Gland Neoplasms↗
PubMed1987

Characterization of sulfated glucuronic acid containing glycolipids reacting with IgM M-proteins in patients with neuropathy.

In some patients with neuropathy and plasma cell dyscrasia, the serum IgM M-proteins are known to bind to the myelin associated glycoprotein and to peripheral nerve glycolipids. We have isolated two acidic glycolipids which bind to the M-protein from human cauda equina by DEAE-Sephadex, Iatrobeads, and high performance liquid column chromatographies. The major acidic glycolipid migrated between GM1 and GD1a and the minor acidic glycolipid migrated between GD1a and GD1b. Their structures were elucidated by sugar analysis, enzymatic digestion, mild acid hydrolysis, permethylation, fast atom bombardment mass spectrometry, and NMR studies. Their core structure was confirmed to be paragloboside by high performance thin-layer chromatography-immunostaining using anti-paragloboside monoclonal antibody. Both acidic glycolipids lacked sialic acid but contained sulfated glucuronic acid as their acidic moiety. The sulfate group in the glucuronic acid was established by periodate oxidation and permethylation studies to be attached to the 3 position. The structures of the two acidic glycolipids are therefore consistent with the following: IV3GlcUA(3-sulfate)nLcOse4Cer and VI3GlcUA(3-sulfate)nLcOse6Cer. Additionally, the free carboxyl group on the glucuronic acid residue was shown to be necessary to bind the IgM M-proteins from neuropathy patients.

Antibodies, Monoclonal↗
PubMed1987

Subcellular localization of sulfated glucuronic acid-containing glycolipids reacting with anti-myelin-associated glycoprotein antibody.

Peripheral nerve glycolipids, with which anti-myelin-associated glycoprotein (MAG) antibodies from patients with demyelinating neuropathy and plasma cell dyscrasia cross-react, proved to be novel glycosphingolipids containing a sulfated glucuronyl residue. Consequently, there has been much interest in the immunological role that these sulfated glucuronyl-glycosphingolipids (SGGLs) may play in the pathogenesis of this disorder. For the determination of the distribution of these glycolipids in various nervous tissues and, thereby, the elucidation of their pathogenicity, a quantitative immunostaining-TLC method for their detection has been devised. Using this method, we demonstrated that these glycolipids were distributed in greatly different amounts in the peripheral nerves from human, bovine, chicken, rat, and rabbit. Subcellular localization studies of bovine peripheral nerve also demonstrated that they were enriched in the axolemma-enriched fraction and present in glial-related membranes in lower concentrations. In addition, these glycolipids were present in bovine dura mater and transformed rat Schwann cells. These biochemical results suggest that not only myelin but also axons could be involved as targets of the anti-MAG antibody in macroglobulinemia neuropathy, and it may also be necessary to examine anti-SGGL activity in patients with axonal neuropathy associated with plasma cell dyscrasia.

Animals↗
PubMed1987

Analysis of B cell dysfunction in patients with common variable immunodeficiency by using recombinant interleukin 2.

Recombinant interleukin 2 (RIL2) induces proliferation and differentiation of the Staphylococcus aureus Cowan I (SAC)-activated normal B cells to immunoglobulin (Ig) producting cells. We applied this finding to an analysis of heterogeneity in the differentiation states of B cells in patients with common variable immunodeficiency (CVI). B cells from 5 of 7 patients with CVI were tested for their ability to proliferate under the stimulation of SAC, or SAC and RIL2, and for their differentiation to Ig producing cells in the presence of SAC plus RIL2. The results suggest that the differentiation status of B cells in CVI could be divided into four states based on their responses to SAC and RIL2. In the first state, no B cell proliferation or differentiation was demonstrated in our assays. B cells in the second state showed normal proliferative responses to SAC, but not to SAC plus RIL2, and no differentiation to Ig-secreting cells. The third state showed normal proliferation in response to SAC and SAC plus RIL2, but no differentiation to Ig-secreting cells. The fourth state had a normal proliferation response to SAC and SAC plus RIL2, and normal secretions of IgG and IgM in response to SAC and RIL2. These results show that some B cells in CVI have defects in response to RIL2, and at least in terms of defect of B cells, CVI is heterogeneous.

B-Lymphocytes↗
PubMed1987

Isolation and characterization of ganglioside GM1b from normal human brain.

A sialidase-susceptible monosialoganglioside was isolated from normal human brain by DEAE-Sephadex A-25 and Iatrobeads column chromatography. The yield of this ganglioside was about 6 mg per whole brain. Its structure was elucidated by sugar analysis, sialidase digestion, permethylation, and proton NMR studies. This ganglioside had carbohydrate, fatty acid, and long-chain base compositions identical to those of brain GM1a. However, the sialosyl residue was found to be linked (alpha 2-3) to the terminal galactosyl residue of the asialo-GM1a backbone. The complete structure of this ganglioside was therefore identified as GM1b or IV3NeuAcGgOse4Cer.

Adult↗
PubMed1986

Impaired monocyte function in glycogen storage disease type Ib.

Phagocyte (neutrophil and monocyte) function was evaluated in a boy with glycogen storage disease type Ib. Neutrophils were found to be defective in motility and respiratory burst and monocytes showed a defect in respiratory burst but not in motility. These results suggested that the glucose-6-phosphate transport system plays a role in the function of neutrophils and monocytes and that these two phagocytes are different from each other in their energy metabolism for motility.

Adolescent↗
PubMed1986

[Application of NMR-CT in the staging of cancer of the digestive organs].

To assess the potential of NMR-CT for demonstrating cancer of the digestive organs, we examined a total of 232 patients (89 with esophageal cancer, 52 with liver cancer, 40 with colorectal cancer, 9 with pancreatic cancer, 9 with gastric cancer, and 33 with other diseases). NMR-CT has many features, but we use especially those features which it is possible to select not only in the transverse plane but also in the coronal and sagittal planes, and it has excellent soft tissue contrast resolution. Our machine is a Picker International NMR-CT using a superconducting magnet of 0.256 tesla. Diagnosis of lymph node involvement of esophageal cancer. Using only the coronal plane, each patient was scanned by the spin echo technique (TE = 40, TR = 400) from the plane of the descending aorta to the plane of the trachea 1 cm in thickness, at 1 cm intervals, continuously. All the vessels were clearly differentiated as no-signal regions, especially in coronal images, from areas of carcinomatous involvement. Lymph nodes were identified as intense grey masses in fat tissue of high intensity. Twenty cases were proved by surgery or autopsy, and it was possible to assess 160 lymph-node groups. A total of 25 patients were imaged as having positive lymph nodes, but 17 of them had metastasis-positive nodes. In other 135 nodes imaged as negative lymph nodes, only two had metastasis and 133 were negative for metastasis. Overall accuracy was 93.8%. Diagnosis of liver cancer. Intrahepatic vessels were clearly imaged without using contrast enhancement in NMR-CT, so it was easy to diagnose the segment containing the tumor and to detect tumor emboli in the portal vein. The capsule was imaged in 84% (16/19) using IR techniques, although only 37% (7/19) could be imaged by X-CT. Diagnosis of colorectal cancer. Using the sagittal plane, the sacrum, urinary bladder and other organs were imaged better parallel to their axis, so that the relationship between rectal cancer and surrounding organs could be clearly visualised with NMR-CT. With regard to lymphatic metastasis, coronal imaging was useful for picturing mesenteric and pelvic vessels, so that lymph nodes were imaged as low-intensity masses along the vessels. Lymph metastasis almost 1 cm size can be detected using coronal NMR-CT.

Digestive System Neoplasms↗
PubMed1985

Molecular parameters and conformation of globoside and asialo-GM1.

Comparative studies of the individual properties and intermolecular organization of asialo-GM1 (Gg4Cer) and globoside (Gb4Cer) were made employing lipid monolayers and high-sensitivity differential scanning calorimetry. The surface pressure-area isotherm of Gb4Cer is more expanded than that of Gg4Cer. This results in greater molecular areas and compressibilities, and lower intermolecular interaction energies, for Gb4Cer compared to Gg4Cer at all surface pressures. This looser intermolecular packing may be responsible for a lower transition temperature (40.5 degrees C) and enthalpy of transition (delta Hcal) (2.0 kcal mol-1) found for the phase transition of Gb4Cer compared to Gg4Cer (54.0 degrees C and 4.2 kcal mol-1). The surface potential per molecule and resultant molecular dipole moment vector values are greater for Gb4Cer than for Gg4Cer at comparable values of surface pressure and molecular area. All these results reflect the existence of a rigid L-shape in the oligosaccharide chain of Gb4Cer that prevents a close intermolecular packing compared to the straight orientation of the polar head group of Gg4Cer. Significant movements of the oligosaccharide chain may occur depending on the lateral surface pressure. At low surface pressures the orientation of the oligosaccharide chain of Gg4Cer may be displaced an angle of up to about 40 degrees compared to the perpendicular position adopted at high surface pressures. In agreement with an enhanced liquid character of the interface, the oligosaccharide chain of Gb4Cer exhibits a greater freedom of movement and the displacement from the position perpendicular to the interface can reach to about 65 degrees.

Chemical Phenomena↗
PubMed1985

Thermotropic behavior of binary mixtures of dipalmitoylphosphatidylcholine and glycosphingolipids in aqueous dispersions.

The thermotropic behavior of mixtures of dipalmitoylphosphatidylcholine (DPPC) with natural glycosphingolipids (galactosylceramide, phrenosine, kerasine, glucosylceramide, lactosylceramide, asialo-GM1, sulfatide, GM3, GM1, GD1a, GT1b) in dilute aqueous dispersions were studied by high sensitivity differential scanning calorimetry over the entire composition range. The pretransition of DPPC is abolished and the cooperativity of the main transition decreases sharply at mole fractions of glycosphingolipids below 0.2. All systems exhibit non-ideal temperature-composition phase diagrams. The mono- and di-hexosylceramides are easily miscible with DPPC when the proportion of glycosphingolipids in the system is high. A limited quantity (1-6 molecules of DPPC per molecule of glycosphingolipid (GSL) can be incorporated into a homogeneously mixed lipid phase. Domains of DPPC, immiscible with the rest of a mixed GSL-DPPC phase that shows no cooperative phase transition, are established as DPPC exceeds a certain proportion in the system. One negative charge (sulfatide) or four neutral carbohydrate residues (asialo-GM1) in the oligosaccharide chain of the glycosphingolipids results in phase diagrams exhibiting coexistence of gel and liquid phases over a broad temperature-composition range. Systems containing gangliosides show complex phase diagrams, with more than one phase transition. However, no evidence for phase-separated domains of pure ganglioside species is found. The thermotropic behavior of systems containing DPPC and glycosphingolipids correlates well with their interactions in mixed monolayers at the air/water interface.

Calorimetry, Differential Scanning↗