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Biomedical subjects

T Takai

Publications and source records attributed to T Takai.

174 records · Page 10Linked to original sources

Induction of antigen-specific IgE response in murine lymphocytes by IL-10.

When murine spleen cells that had been primed with trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) were stimulated in vitro with the same antigen, anti-TNP IgE, as well as anti-TNP IgM and IgG1, was secreted into the culture medium. On the other hand, anti-TNP IgM and IgG1 were produced, but anti-TNP IgE secretion was negligible when the carrier (KLH)-primed spleen cells were cultured with the hapten-carrier antigen (TNP-KLH) under the same conditions. Anti-TNP Ig responses in the latter cultures are thought to reflect the interaction between normal TNP-specific B cells and KLH-primed helper T cells. By using this culture system, we investigated the requirements of exogenous cytokines for inducing anti-TNP IgE response. The addition of interleukin-4 (IL-4), that is known to induce IgE response in LPS-stimulated murine B cells, failed to elicit anti-TNP IgE response. The combination of IL-4 with IL-2 and/or IL-5 was also ineffective. Interestingly, a significant level of anti-TNP IgE was induced when IL-10, another cytokine from type 2 helper T cells, was added to the culture. Although IL-10 enhanced the production of anti-TNP IgM and IgG1, as well as that of anti-TNP IgE, the rate of enhancement was at least 3-fold higher in the IgE response than in the IgM and IgG1 responses. Simultaneous addition of IL-4, IL-5 or IL-13 with IL-10 did not augment but rather reduced the enhancing effects of IL-10. IL-10 did not further stimulate the spontaneous secretion of IgE from antigen-primed B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Non-anaphylactic combination of partially deleted fragments of the major house dust mite allergen Der f 2 for allergen-specific immunotherapy.

Allergen-specific immunotherapy, in which repeated injections of allergens over prolonged periods are used to induce tolerance, has proven an effective treatment of allergy. A major side effect of allergen-specific immunotherapy is anaphylactic reaction. House dust mite allergens are major causative factors associated with various allergic diseases. Der f 2 is the major house dust mite allergen composed of 129 amino acid residues. Analysis using deletion mutants of Der f 2 suggested that T-cell epitopes of Der f 2 were multiple in mite-allergic patients. We found that some IgE epitopes were renatured by dialysis of a mixture of two denatured C- and N-terminal deletion mutants, 1-112 and 85-129 in 13 patients out of 14. On the other hand, IgE binding activity was negative in the separately dialyzed fragments and their mixture in each patient tested. Furthermore, we demonstrated that neither of the two separately prepared polypeptides induced in vivo skin prick test reactivity. These findings are important for improvement of T-cell targeting allergen-specific immunotherapy and development of monovalent IgE haptens. The use of combinations of overlapping non-anaphylactic fragments of allergen covering all of the T-cell epitopes achieves the removal of IgE reactivity, the cause of harmful anaphylactic reactions, without affecting the T-cell reactivity essential for immunotherapy, offering potentially safer and more effective treatment for allergic disease.

Allergens↗

Isolation and structural organization of the human preproenkephalin B gene.

The primary structure of porcine preproenkephalin B has been elucidated by cloning and sequencing cDNA: it contains neoendorphin, dynorphin and leumorphin (containing rimorphin as its amino-terminus). These opioid peptides, each having a leucine-enkephalin structure, act on the kappa-receptor. We have now cloned a human genomic DNA segment containing the preproenkephalin B gene. The structural organization of this gene resembles those of the genes encoding the other opioid peptide precursors, that is, preproenkephalin A and the corticotropin-beta-lipotropin precursor (ACTH-beta-LPH precursor). The primary structure of human preproenkephalin B has been deduced from the gene sequence. The amino acid sequence homology observed between preproenkephalin B and preproenkephalin A, together with the similarity between their gene organizations, suggests that the two genes have been generated from a common ancestor by gene duplication.

Amino Acid Sequence↗

Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.

Cloning and sequence analysis of cDNA for the Electrophorus electricus electroplax sodium channel indicate that this protein, consisting of 1,820 amino acid residues, exhibits four repeated homology units, which are presumably oriented in a pseudosymmetric fashion across the membrane. Each homology unit contains a unique segment with clustered positively charged residues, which may be involved in the gating structure, possibly in conjunction with negatively charged residues clustered elsewhere.

Amino Acid Sequence↗

Cloning, sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle.

The nicotinic acetylcholine receptor (AChR) from fish electric organ has a subunit structure of alpha 2 beta gamma delta, and this is thought to be also the case for the mammalian skeletal muscle AChR. By cloning and sequencing the complementary or genomic DNAs, we have previously elucidated the primary structures of all four subunits of the Torpedo californica electroplax and calf muscle AChR and of the alpha- and gamma-subunits of the human muscle AChR; the primary structures of the gamma-subunit of the T. californica AChR and the alpha-subunit of the Torpedo marmorata AChR have also been deduced elsewhere. We have now cloned DNA complementary to the calf muscle messenger RNA encoding a novel polypeptide (the epsilon-subunit) whose deduced amino-acid sequence has features characteristic of the AChR subunits and which shows higher sequence homology with the gamma-subunit than with the other subunits. cDNA expression studies indicate that the calf epsilon-subunit, as well as the calf gamma-subunit, can replace the Torpedo gamma-subunit to form the functional receptor in combination with the Torpedo alpha-, beta- and delta-subunits.

Amino Acid Sequence↗

Role of acetylcholine receptor subunits in gating of the channel.

The Torpedo and calf acetylcholine receptors and hybrids composed of subunits from the two species have been produced in Xenopus oocytes by the use of the cloned complementary DNAs. Single-channel current measurements indicate that these receptors form channels of similar conductance but with different gating behaviour.

Animals↗

Molecular distinction between fetal and adult forms of muscle acetylcholine receptor.

Distinct classes of acetylcholine receptor channels are formed when Xenopus oocytes are injected with combinations of the bovine alpha-, beta-, gamma- and delta- or the alpha-, beta-, gamma- and epsilon-subunit-specific messenger RNAs. The conductance and gating properties of the two classes of channels, in conjunction with the developmental changes in the muscular contents of the mRNAs, suggest that replacement of the gamma-subunit by the epsilon-subunit is responsible for the functional alteration of the receptor during muscle development.

Animals↗

Development of the receptor database (RDB): application to the endocrine disruptor problem.

MOTIVATION: To represent various aspects of receptors effectively, we developed the receptor database (RDB), using an object-oriented database management system ACEDB and the Internet/WWW technology. RESULTS: RDB was constructed so that the system collects data items such as attributes of proteins from distributed data sources of the Internet, and so that it provides various viewing tools effectively, depending on different types of receptor data. Such sources include standard international biological databases such as the up-to-date database of PIR, Swiss Prot, PDB, GenBank and GDB. Application to the endocrine disruptor problem is presented. AVAILABILITY: RDB is available through the Internet at http://impact.nihs.go.jp/RDB.html.

Amino Acid Sequence↗

Type 2 segmental manifestation of disseminated superficial porokeratosis showing a systematized pattern of involvement and pronounced cancer proneness.

Nine tumors of squamous cell carcinoma developed in a 61-year-old Japanese woman with linear porokeratosis. She had disseminated superficial porokeratosis, but a linear arrangement of pronounced lesions was found only on the left side of the body, and all of the tumors arose on the linear lesions on the left side of the body. Some of her family members had disseminated superficial porokeratosis. This case may represent a type 2 segmental manifestation of disseminated superficial porokeratosis showing a systematized pattern of involvement and pronounced cancer proneness.

Carcinoma, Squamous Cell↗

A case of AFP-producing early gastric carcinoma with rapid growth liver metastasis.

An 84-year-old man presented with complaints of epigastric discomfort. Upper gastrointestinal series and endoscopy showed an elevated lesion at the posterior wall of greater curvature on the gastric fundus. Diagnosed as moderately differentiated tubular adenocarcinoma by biopsy, wedge resection and 4sa regional lymph node dissection were carried out. The tumor morphology showed type I with slight elevation, 2.5 x 1.7 cm in size; histological showed papillary, tubular, and solid formations having clear cytoplasm and large bizarre nuclei invading the deep submucosal layer (sm2). This case was evaluated as T1(sm) N0 M0 stage Ia early gastric cancer. In the 5th month after operation, multiple liver metastases were detected. He died of liver failure by rapid growth of metastatic tumors in the 6th month after operation. The serum alpha-fetoprotein level at recurrence was 1,900 ng/mL, and alpha-fetoprotein-positive cells were immunohistochemically detected in operative and liver biopsy specimens.

Aged↗

Effect of fat emulsion in patients with liver disorders.

The effect of fat emulsion in preoperative patients (n = 17) with liver disorders was studied by liver-function tests, intraoperative liver biopsy specimens, intravenous fat tolerance tests, and serum fatty acid analyses. There was no difference between liver-function tests before and after the administration of fat emulsion. Before the administration of fat emulsion, the levels of serum lipids were relatively low, and serum fatty acid patterns were abnormal. However, after the administration of fat emulsion, serum lipid levels increased, and serum fatty acid patterns became nearly normal. There was a significant correlation between the total fat intake and serum linoleic acid change before and after the administration of fat emulsion. From this equation, the total fat intake required for a normal range of serum linoleic acid was calculated to be 7 g/kg fat. These results suggest that the administration of fat emulsion improves serum fatty acid patterns without a deterioration of liver function in preoperative patients with liver disorders, but total intake of 10% fat emulsion greater than 70 ml/kg might induce higher serum fatty acids than in healthy control subjects and cause overload in these patients.

Adult↗