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Biomedical subjects

A Yachi

Publications and source records attributed to A Yachi.

At least 73 records · Page 4Linked to original sources

[Immunological study on Alzheimer's disease using anti-beta-protein monoclonal antibodies].

Monoclonal antibodies (TB1 & TB2), which were obtained by immunization of 24 amino acids in BALB/c mice, bound specifically to the amyloid senile plaque and amyloid-angiopathic lesions of brain tissues of patients with Alzheimer's disease (AD) or with senile dementia of Alzheimer type (SDAT), and strongly reacted with the 1st part (Asp-Ala-Glu-Phe-Arg-His-Asp) of beta-protein. Western blotting and two-dimensional immunoelectrophoresis of cerebrospinal fluid (CSF) and serum revealed bands of 125 and 20 kilodaltons. The positive frequency of 125 and 20 KD bands detected by two-dimensional immunoelectrophoresis was higher in the serum of AD and SDAT patients (12 cases) than in that of normal control patients. ELISA employing various anti-amyloid precursor protein (APP) antibodies was performed using the extract of the human neuroblastoma cell line (NB39) which produces APP. In the near future, we hope to measure APP in CSF and sera from patients with Alzheimer's disease.

Aged↗

[Effects of rHuEPO on aplastic anemia: results of a phase II clinical study].

The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in adult aplastic anemia patients whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously every day at a dose of 3,000IU/body for two weeks, and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. In cases in whom Hb concentration increased by more than 1g/dl or whose transfusion requirements reduced to less than 50%, treatment was judged to be effective. The whole rate of efficacy was 34.5% (10/29). Response to epoetin alpha treatment was better in patients whose symptoms were relatively mild. Mild cases responded to the treatment with 6,000IU/body/day, although a dosage of 24,000IU/body/day was required in moderate or severe cases. Neither serious adverse effect nor abnormal laboratory findings were observed. These results suggest that high dose subcutaneous epoetin alpha treatment is effective for the aplastic anemia in terms of increasing Hb concentration and reducing blood transfusions.

Adolescent↗

[Phase II clinical study of recombinant human erythropoietin on the anemia associated with multiple myeloma].

Safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with multiple myeloma whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha (3,000IU/body) was given subcutaneously daily for two weeks and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. Cases in which Hb concentration increased by more than 1g/dl or in which blood transfusion requirements decreased by more than 50% were judged to be effective. The overall rate of efficacy was 52.6% (10/19). Response to epoetin alpha treatment was better in patients whose blood erythropoietin level was relatively low. The majority of patients responded to the treatment with up to 6,000IU/body/day but a dosage of more than 12,000IU/body/day was required in some cases. No serious adverse effects or abnormal laboratory findings were observed. These results suggest that high-dose subcutaneous epoetin alpha treatment is effective for anemia associated with multiple myeloma in terms of increasing Hb concentration and reducing blood transfusion.

Aged↗

[Phase II clinical study of recombinant human erythropoietin on the anemia of myelodysplastic syndrome].

The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with myelodysplastic syndrome (MDS) whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously daily at a dose of 3,000IU/body for two weeks and the dosage was increased to 6,000IU, 12,000IU, and 24,000IU at two week interval when the increment of Hb was insufficient. Patients in whom the Hb concentration increased by more than 1g/dl or whose blood transfusion requirement reduced to below 50% were considered to be cases of effective treatment. The overall rate of effectiveness was 20.6% (7/34). Response to epoetin alpha treatment was better in patients with refractory anemia (RA) or RA with ringed sideroblasts (RARS). The high dose epoetin alpha (12,000-24,000IU/body/day) was required for the patients to respond. These results suggest that the high dose subcutaneous epoetin alpha treatment is effective for the anemia associated with MDS in terms of increasing Hb concentration and reducing blood transfusion.

Adolescent↗

Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2.

Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity.

Amino Acid Sequence↗

Cloning and characterization of a human cDNA encoding a novel putative cytoplasmic protein-tyrosine-phosphatase.

We have cloned and characterized a human cDNA encoding a new member of the family of cytosolic type protein-tyrosine-phosphatase (PTP), designated as PTPG1, from an adult colon tissue cDNA library by using the PCR product as probe. We obtained 5 cDNA clones, which cover the predicted open reading frame encoding a 88-kDa protein composed of 780 amino acids, and it had no apparent signal or transmembrane sequences, suggesting that it is a cytosolic protein. The N-terminal region had a PTP catalytic domain that is 30-40% identical to previously reported human PTPs. This revealed that the enzyme composes an additional family of human PTPs. PTPG1 was characterized by a long non-enzymatic domain located at the C-terminus, including PEST sequences which are characteristic for short half-life proteins in eukaryotes. Northern blot analysis of PTPG1 mRNA showed a 4.6-kb transcript that was detected in a wide variety of cell lines to suggest its extensive expression.

Amino Acid Sequence↗

Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP.

We isolated cDNA clones encoding a protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 40-kDa protein composed of 360 amino acids and has no apparent hydrophobic segments, suggesting that it is a nontransmembrane PTP, which was designated as LC-PTP (leukocyte PTP). Northern blot analysis revealed that the LC-PTP mRNA was preferentially expressed in a variety of hematopoietic cells and the transcriptional sizes were approximately 4.0 kilobases and approximately 2.9 kilobases. Fluorescent in situ hybridization revealed that the human LC-PTP gene is located on the chromosome region 1q32.1, which is known to be a site associated with chromosomal deletion in malignant lymphomas, where candidate tumor suppressor genes might be present.

Amino Acid Sequence↗

[A case of latent Addison's disease with hypogonadotropic hypogonadism and dwarfism].

A case of latent Addison's disease accompanied by hypogonadotropic hypogonadism and dwarfism is described. A 20-year-old man was admitted to our department complaining of short stature and immature development of the external genitalia. Pigmentation was most evident on the fingers and face. Endocrinologically, serum ACTH level was very high, and serum cortisol level was in the lower limit of the normal range. Serum aldosterone and adrenal androgen levels were below their normal ranges. Based on these clinical and laboratory findings, the patient was diagnosed as having latent Addison's disease. Serum LH did not respond to a bolus injection of LH-RH. However, after 3 days administration of LH-RH, the response of serum LH to a bolus injection of LH-RH was enhanced. Serum testosterone level was not increased after the administration of hCG. These findings suggested a hypothalamic cause for the hypogonadism. It was indicated that short stature was apparently caused by GH neurosecretory dysfunction, since nocturnal GH secretion was below that in normal males and the response of GH to the administration of arginine was normal. In regard to the thyroid function, the peak of serum TSH after a bolus injection of TRH was delayed compared with normal subjects, and although serum T4 level was high, the basal metabolic rate was very low. This suggests that there is tissue resistance to the elevated thyroid hormone.

Addison Disease↗

Protein-tyrosine phosphatase expression in pre-B cell NALM-6.

Protein-tyrosine phosphatase (PTP)-related complementary DNAs from NALM-6 (pre-B cell line) were amplified by reverse transcriptase polymerase chain reaction using primers corresponding to the conserved catalytic domains of PTPs. Thirty-three polymerase chain reaction products, identified as PTP related complementary DNAs, were classified to RPTP-alpha, PTP1B, and 4 novel PTPs, which were designated as BPTP-1-4. Their expressions in NALM-6 and other cell lines were confirmed by Northern blot analysis. BPTP-1 and -2 exhibited extensive homology with the first and the second catalytic domains, respectively, of leukocyte common antigen related molecule (LAR) and human PTP delta. The transcriptional sizes of BPTP-1 and BPTP-2 are the same (7.2 kilobases) as that of LAR. The expression of BPTP-1 was abundant in lymphoid cell lines TALL-1 and NALM-6 but small in colon cell line BM314, which is in sharp contrast to the expression of LAR. These data suggest that the expression levels of BPTP-1 and LAR are altered in a cell specific manner, probably making them cell type associated PTPs.

Amino Acid Sequence↗

Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease.

OBJECTIVE: We investigated whether levels of intercellular adhesion molecule 1 (ICAM-1) antigen shed into the circulation increase during acute Kawasaki disease (KD). We also compared ICAM-1 levels in acute KD with those in anaphylactoid purpura (AP) and in measles. METHODS: Serum ICAM-1 levels were measured by a double-determinant immunoassay using 2 monoclonal antibodies in the FAST (Falcon assay screening test) system. Serum levels of tumor necrosis factor alpha (TNF alpha) were measured by a specific and sensitive sandwich enzyme immunoassay. RESULTS: Patients with KD, but not those with AP or measles, had increased levels of shed ICAM-1 antigen in serum samples obtained during acute stages. Moreover, during the acute stage, KD patients with coronary artery lesions (CAL) had still higher levels of shed ICAM-1 than did those without CAL. We found a positive correlation between serum levels of shed ICAM-1 and levels of TNF alpha during acute KD. CONCLUSION: Our findings suggest that the serum ICAM-1 level is an important immunologic parameter for determining the severity of vascular damage during acute KD.

Cell Adhesion Molecules↗

Adult T-cell leukemia/lymphoma (lymphoma type) with remarkable gastric lesions: a case report.

We report a case of a 53-year-old woman with adult T-cell leukemia/lymphoma (ATL) (lymphoma type) with multiple gastric lesions, admitted to our hospital because of systemic lymphadenopathy and epigastralgia. Gastroscopy showed a variety of gastric lesions including thickened folds, ulcerations and polypoid lesions. Biopsy specimens obtained from the stomach and lymph nodes revealed diffuse infiltration of pleomorphic mononuclear cells and the integration of HTLV-1 proviral DNA. We demonstrated through the investigation of 30 previously reported cases of ATL that this is a rare case of the lymphoma type of ATL presenting remarkable gastric lesions.

Blotting, Southern↗

Circulating tumor-associated antigens detected by monoclonal antibodies against the polypeptide core of mucin--comparison of antigen MUSE11 with CA15-3.

The antigen MUSE11 detected by a monoclonal antibody (MAb) is an adenocarcinoma-associated antigen, while CA15-3 is a representative breast cancer-associated antigen detected by MAbs 115D8 and DF3. MAb MUSE11 showed higher binding activity to a synthetic peptide corresponding to the tandem repeat motif of the mucin core protein than that of MAb DF3, although MAb DF3 also had a significant binding activity indicating that MAbs MUSE11 and DF3 could recognize an identical polypeptide core. The reactivity of MAb DF3 to a breast cancer cell line MRK-neu-1 was completely abolished by neuraminidase treatment whereas that of MAb MUSE11 was partly conserved. The simultaneous measurement of the antigens MUSE11 and CA15-3 in sera from 35 cancer patients demonstrated that the incidence of abnormal serum level of CA15-3 was lower than that of antigen MUSE11. These data suggest that at least a part of the structural basis for the difference between the serum levels of antigen MUSE11 and CA15-3 could be carbohydrate side chains including sialic acids.

Antibodies, Monoclonal↗

Circulating intercellular adhesion molecule-1 (ICAM-1) antigen in sera of patients with idiopathic pulmonary fibrosis.

Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene family with a five-domain structure, is known to play an important role in inflammatory diseases. An ELISA was developed using two MoAbs against human ICAM-1 in order to detect the soluble shedding ICAM-1 antigen in sera. We measured levels of circulating ICAM-1 antigen in sera of patients with idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis, hypersensitive pneumonitis, bacterial and mycoplasmal pneumonia, and inflammatory diseases of other organs. The results clearly demonstrated that IPF had significantly high levels of circulating ICAM-1 in sera as compared with other disorders or normal controls. Moreover, immunohistochemical analysis with MoAb against human ICAM-1 disclosed that in IPF, the expression of ICAM-1 was intensively enhanced on alveolar epithelial cells. These results suggest that ICAM-1 may contribute to the pathogenesis of IPF.

Adult↗