Search PubMed⌕ Search

Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 937 records · Page 52Linked to original sources

Specificity of the T cell immune response to acetylcholine receptor in experimental autoimmune myasthenia gravis. Response to subunits and synthetic peptides.

Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are T cell-dependent diseases mediated by antibodies against acetylcholine receptor (AChR) on skeletal muscle. Most of the antibodies are directed toward conformation-dependent epitopes on the AChR, whereas T cells recognize denatured AChR. In search of T cell epitopes in EAMG, we tested 24 synthetic peptides covering 62% of the alpha-subunit sequence of Torpedo californica electric organ AChR in the T cell proliferation assay with lymph node cells from rats immunized with AChR. In Lewis rats, 2 of these peptides, [Tyr 100]alpha 100-116 and [Gly 89, Tyr 90]alpha 73-90, strongly stimulated T cells and, of these, [Tyr 100]alpha 100-116 was much more potent; 4 other peptides were weakly mitogenic and 18 were ineffective. None of the 24 synthetic peptides alone stimulated anti-AChR production and, when added to cultures along with AChR, [Tyr 100]alpha 100-116 and [Gly 89, Tyr 90]alpha 73-90 suppressed antibody production. Of twelve cloned T cell lines specific to AChR, 4 responded to [Tyr 100]alpha 100-116, indicating the importance of the epitope in alpha 101-116 in Lewis rats. In three other strains of rats whose responses to AChR and its subunits were similar to those in the Lewis rat, neither [Tyr 100]alpha 100-116 nor [Gly 89, Tyr 90]alpha 73-90 was stimulatory. Instead, completely different sets of peptides stimulated their T cells. When peptides were used as immunogens, each strain (except Lewis rats) responded only to the peptides that stimulated AChR-immune T cells from the same strain. Genetically restricted T cell recognition of AChR peptides in rats suggests that T cells from MG patients with different major histocompatibility haplotypes may recognize different AChR peptides.

Amino Acid Sequence↗

Parathyroid hormone control of free cytosolic Ca2+ in the kidney.

We have established a perifusion system to monitor free cytosolic calcium concentrations ([Ca2+]i) in mouse kidney slices, which presumably reflects in vivo status more accurately than renal cells in culture, by means of the fluorescent calcium indicators quin-2 and fura-2. An increase in the extracellular calcium concentrations from 0 (no added Ca2+) to 3.0 mM resulted in an increase in [Ca2+]i from 52 to 239 nM. Replacement of 118 mM of extracellular Na+ with choline, or the addition of ouabain, an inhibitor of Na+,K+-ATPase, at 10(-6) M in the perfusate caused an increase in [Ca2+]i from 161 +/- 13 to 873 +/- 78 nM (n = 10) and 161 +/- 13 to 395 +/- 68 nM (n = 4), respectively, suggesting the possible existence of a Na+,Ca2+ exchange mechanism in the kidney slice. We further examined the effects of PTH on [Ca2+]i mobilization in the kidney. Both human PTH-(1-34) and hPTH-(1-84) increased [Ca2+]i within 60 s at physiologic concentrations of 10(-11)-10(-9) M in a dose-dependent manner. On the other hand, an increase in intracellular cAMP in the slice was also detected above 3 X 10(-9) M hPTH-(1-34) [base 2.1 +/- 0.4 pmol/mg, 3.2 +/- 0.6 pmol/mg (p less than 0.05 versus control values) 5 minutes after the application of 3 X 10(-9) M hPTH-(1-34) and 17.3 +/- 4.3 pmol/mg (p less than 0.05 versus control values) 3 X 10(-8) M hPTH-(1-34), mean +/- SEM, n = 7, p less than 0.05 versus control values].(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗

The characteristics of thymoma with myasthenia gravis: a 28-year experience.

Of 134 patients with thymoma, 79 (59%) also had myasthenia gravis (MG). The thymoma with MG differed from that in the absence of MG in the following aspects: The ratio of lymphocytes to epithelial cells in the tumor was larger, the polygonal cell type was more prominent (i.e., in 83% of the MG patients this cell type predominated), and the differentiation of epithelial cells in the tumor was more advanced in the group with MG than in the group without MG. Furthermore, the clinical stage of thymoma was earlier, the recurrence rate was lower, and the survival curve was better in the group with MG than in the group without MG. These findings suggest that the thymoma with MG is less malignant than that without MG.

Adolescent↗

Cat scratch disease. An epidemiological and ultrastructural study of lymphadenitis caused by Warthin-Starry positive bacteria.

The aetiological agent of cat scratch disease (CSD) has been unknown for more than 30 years. Recently, a micro-organism clearly shown with Warthin-Starry silver (W-S) stain was found and thought to be a possible cause of the disease. In this study, 32 cases of regional lymphadenopathy histologically compatible with CSD and 20 contrasting cases of lymphadenopathy were examined retrospectively with W-S stain. W-S positive pleomorphic organisms were clearly demonstrated in 20 of the 32 suspected cases of CSD, but in none of the other cases. The onset of disease in these 20 cases with W-S positive organisms occurred between July and January. This seasonal variation in the onset of disease was highly significant (P less than 0.005) and was not due to a single epidemic. Moreover, some characteristic morphological features of the organism were found by electron microscopic observations. Ultrastructurally, the organism was a bacterium showing a chain-like arrangement, septal formation, branching and clubbed ends.

Abscess↗

Structural similarity of bovine lung prostaglandin F synthase to lens epsilon-crystallin of the European common frog.

Cloned cDNA sequences specific for prostaglandin F (PGF) synthase have been isolated from a cDNA library of bovine lung mRNA sequences. Nucleotide-sequence analyses of cloned cDNA inserts have revealed that PGF synthase consists of a 969-base pair open reading frame coding for a 323-amino acid polypeptide with a Mr of 36,666. The sequence analysis indicates that bovine lung PGF synthase shows 62% identical plus conservative substitutions compared with human liver aldehyde reductase [Wermuth, B., Omar, A., Forster, A., Francesco, C., Wolf, M., Wartburg, J.P., Bullock, B. & Gabbay, K.H. (1987) in Enzymology and Molecular Biology of Carbonyl Metabolism: Aldehyde Dehydrogenase, Aldo-Keto Reductase, and Alcohol Dehydrogenase, eds. Weiner, H. & Flynn, T.G. (Liss, New York), pp. 297-307], which is similar to PGF synthase in molecular weight and substrate specificity. However, comparison of the amino acid sequence of PGF synthase with the National Biomedical Research Foundation protein data base reveals that the sequences of 225 amino acids from C termini of epsilon-crystallin of the European common frog (Rana temporaria) [Tomarev, S.I., Zinovieva, R.D., Dolgilevich, S.M., Luchin, S.V., Krayev, A.S., Skryabin, K.G. & Gause, G.G. (1984) FEBS Lett. 171, 297-302] and of PGF synthase show 77% identical and conservative substitutions without deletions/additions. The result suggests that European common frog lens epsilon-crystallin is identical to bovine lung PGF synthase.

Aldehyde Oxidoreductases↗

Establishment of a human monoclonal antibody to Hanganutziu-Deicher antigen as a tumor-associated carbohydrate antigen.

We have established a human-human hybridoma producing a monoclonal antibody against a tumor-associated carbohydrate-specific antigen, Hanganutziu-Deicher (HD) antigen. Human spleen lymphocytes from a patient with esophageal varices complicated with liver cirrhosis were cultured in serum-free medium and co-stimulated with both anti-human mu-chain antibodies and supernatants of concanavalin A-stimulated human spleen cell culture (ConA sup). The activated lymphocytes were subsequently primed in vitro with particulate HD3 antigen and fused with a parent hybrid myeloma cell line, KR-12. A hybridoma, 1F43E31G7 produced anti-HD human monoclonal antibody (IgM lambda). This monoclonal antibody reacted strongly with N-glycolylneuraminyl alpha 2-3 lactosylceramide (HD3) and slightly with N-glycolylneuraminyl alpha 2-3 lactoneotetraosylceramide (HD5), but did not react with N-glycolylneuraminyl alpha 2-3 lactoneohexaosylceramide (HD7), N-acetylneuraminyl alpha 2-3 lactosylceramide (GM3) and other derivatives of HD3 prepared by chemical modification of the sialic acid residue of HD3, which indicates that the monoclonal antibody is directed precisely toward the terminal sialic acid and whole structure of HD3.

Antibodies, Anti-Idiotypic↗

A new monoclonal antibody, UFT-4, reacting with rat Kupffer cells. Immunohistochemical and immunoelectron microscopical analysis with reestimation of the reticuloendothelial system.

A new monoclonal antibody, designated UFT-4, reacting with rat Kupffer cells, was produced using sinusoidal liver-cell fraction as an immunogen. Immunohistochemically, UFT-4 reacted with Kupffer cells, interdigitating cells (IDCs), sinus endothelial cells of the spleen, a proportion of reticulum cells, smooth muscle fibers, choroid plexus epithelia and some macrophages. Immunoelectron microscopy disclosed two types of intracytoplasmic positivity: a striated type and a diffuse type. Both appeared to depend on variations in the quantity and distribution of the same antigen. On the other hand, UFT-4 gave a negative result for blood monocytes and most macrophages in lymphatic sinuses, lymphoid follicles, splenic red pulp and loose connective tissue. Cells positive for UFT-4 were mostly considered to belong to a narrow spectrum of the classical reticuloendothelial system, explaining the close relationship existing between some endothelia and some macrophages or reticulum cells. SDS-PAGE analysis of immunoprecipitates showed that the antigen reacting with UFT-4 was of molecule of 36-42 kDa under reducing conditions in the presence of 2-mercaptoethanol. The present results suggest that UFT-4 will be very useful for the study of Kupffer cells and for reconsidering their origin and destination.

Animals↗