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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 451 records · Page 25Linked to original sources

Long-term follow-up by coronary angiography in a patient with heterozygous familial hypercholesterolemia: a case report.

A 47-year-old man with heterozygous familial hypercholesterolemia was followed up by coronary angiography for 9 years. During these 9 years, he experienced inferior myocardial infarction twice, at segment 1 of the right coronary artery. A coronary atherosclerotic lesion (50% stenosis) was also present at segment 6 of the left anterior descending coronary artery. This lesion remained unchanged for the first 7 years, but then rapidly progressed to 90% stenosis in the 8th year. While the rate of the progression of coronary atherosclerosis is generally unpredictable, it may progress rapidly in this case of heterozygous familial hypercholesterolemia.

Angioplasty, Balloon, Coronary↗

[The change of hepatic energy status after transcatheter arterial embolization (TAE) for hepatocellular carcinoma--a study using 31P-MRS].

In six patients with hepatocellular carcinoma, adenosine triphosphate (ATP) phosphomonoester (PME), phosphoric acid (Pi) and pH were measured before and after transcatheter arterial embolization (TAE), using 31P-magnetic resonance spectroscopy (MRS). The effectiveness of TAE was judged by the extent of lipiodol accumulation within the tumor and change in serum alphafetoprotein level. The pH within the tumor decreased 2-9 days after TAE in all the cases, and beta ATP/Pi ratio decreased when TAE was effective, whereas the ratio did not decrease when TAE was ineffective. The beta ATP/Pi ratio measured by 31P-MRS seems to be a useful, non-invasive marker of the anti-tumor effect of TAE, although further investigation is needed.

Adenosine Triphosphate↗

[Chemoradiation therapy for esophageal carcinoma].

Cancer of the esophagus poses a great challenge to the surgical, medical, and radiation professions. Despite standardization of resection and reconstruction techniques, extended lymph node dissection, and advances in perioperative management, the overall prognosis of patients with esophageal cancer undergoing surgical resection has not improved. Preoperative combination chemoradiation therapy in patients with squamous cell esophageal carcinoma has recently received increasing attention, because preoperative chemoradiation therapy, consisting of the concurrent combination of 5-fluorouracil, cis-platinum and radiation, appears to increase the resection rate, the rate of pathological complete responders, and survival time after esophagectomy in patients with locally advanced tumors. Overall in the trials using preoperative concurrent chemoradiotherapy, major antitumor responses have been reported in 40% to 80% of patients, and, consistently, up to 42.1% pathologic complete responses have been seen at esophagectomy. Therefore, preoperative chemoradiation therapy can be anticipated for better prognosis of the patients with locally advanced esophageal cancer.

Carcinoma, Squamous Cell↗

Comparison between the multiplex PCR, sensitivity to biotype specific phages & polymyxin B for biotyping of Vibrio cholerae O1.

A total of 196 Vibrio cholerae O1 strains isolated between 1970 and 1996 were biotyped by multiplex PCR, susceptibility to polymyxin B and sensitivity to biotype specific phages. We modified the multiplex PCR by increasing the primer concentration of tcpA to improve the results. Comparison of the results of modified multiplex PCR and sensitivity to biotype specific phages and to polymyxin B showed that multiplex PCR was as efficient as phage typing for biotyping of V. cholerae O1. All the strains of V. cholerae O1 could be accurately distinguished based on polymyxin B sensitivity. Thus our results show that susceptibility of strains of V. cholerae O1 to polymyxin B is the easiest method to biotype V. cholerae O1 and is feasible in most laboratories when compared with multiplex PCR and sensitivity to biotype specific phages.

Anti-Bacterial Agents↗

Inhaled cromoglycate reduces airway neurogenic inflammation via tachykinin antagonism.

To determine whether sodium cromoglycate (SCG) inhibits airway neurogenic inflammation and, if so, to elucidate the mechanism of its action, we studied plasma extravasation evoked by hypertonic saline in the rat trachea by measuring the amount of extravasated Evans blue dye. Inhalation of hypertonic saline (5-15% NaCl) produced microvascular leakage, an effect that was reduced by pretreatment with SCG in a dose-dependent manner. Inhaled SCG (10 mg/ml) for 2 min did not affect the basal vascular permeability, but significantly inhibited the 10% NaCl-induced plasma extravasation by 34%. SCG likewise inhibited the responses of microvascular leakage to substance P aerosols, whereas it was without effect on those to platelet activating factor aerosols. These results suggest that SCG inhibits airway neurogenic inflammation presumably via functional antagonism of tachykinins, and that this novel effect may be involved in the therapeutic efficacy of SCG in the treatment of airway inflammatory diseases including asthma.

Administration, Inhalation↗

A Case of Breast Cancer Metastatic to the Pituitary Gland.

A case of breast cancer that developed pituitary metastasis 22 years after mastectomy is reported. The pituitary metastasis was associated with hypopituitarism, impairment of the visual field and later diabetes insipidus. The serum levels of CA15-3 and NCC-ST-439, tumor markers of breast cancer, were increased, and CA15-3 (DF3) and NCC-ST-439 were demonstrated in the resected pituitary metastatic lesion immunohistochemically.

Journal Article↗

Autoantibodies to DNA-dependent protein kinase. Probes for the catalytic subunit.

DNA-dependent protein kinase (DNA-PK) is an important nuclear enzyme which consists of a catalytic subunit known as DNA-PKcs and a regulatory component identified as the Ku autoantigen. In the present study, we surveyed 312 patients in a search for this specificity. 10 sera immunoprecipitated a large polypeptide which exactly comigrated with DNA-PKcs in SDS-PAGE. Immunoblot analysis demonstrated that this polypeptide was recognizable by a rabbit antiserum specific for DNA-PKcs. Although the patient sera did not bind to biochemically purified DNA-PKcs in immunoblots or ELISA, they were able to deplete DNA-PK catalytic activity from extracts of HeLa cells in a dose-dependent manner. We conclude that these antibodies should be useful probes for studies which aim to define the role of DNA-PK in cells. Since six sera simultaneously contained antibodies to the Ku protein, these studies suggest that relatively intact forms of DNA-PK complex act as autoantigenic particles in selected patients.

Antigens, Nuclear↗

Significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer in relation to lymph node metastasis.

Proliferating cell nuclear antigen (PCNA) in gastric cancer was evaluated in relation to lymph node metastasis. A total of 125 gastric cancer patients who underwent gastrectomy were studied immunohistochemically. The PCNA-positive rate of the primary lesion with lymph node metastasis (47.6%) was significantly higher than those in those without metastasis (24.3%, P < 0.0001). The PCNA-positive rate of early gastric cancer was significantly higher in lesions with lymph node metastasis (36.9%) than in lesions without lymph node metastasis (14.7%). However, there was no significant difference between lesions with and without lymph node metastasis in advanced gastric cancer. In addition, the PCNA-positive rate in metastatic lesions (44.6%) was significantly higher than that in the primary lesion (40.0%, P = 0.001). It is concluded that gastric cancer with higher tumor growth activity has a higher rate of lymph node metastasis. Cancer cells in the metastatic foci of lymph node have a higher proliferating activity than that in the primary lesion.

Female↗

Autoantibodies to glycyl-transfer RNA synthetase in myositis. Association with dermatomyositis and immunologic heterogeneity.

OBJECTIVE: To elucidate the clinical significance and immunologic heterogeneity of anti-glycyl-transfer RNA (tRNA) synthetase antibodies in polymyositis/dermatomyositis (PM/DM). METHODS: Sera from 345 patients with rheumatic diseases, including 91 with myositis, were examined using immunoprecipitation assays. Autoantibodies to aminoacyl-tRNA synthetases were further analyzed with 2-dimensional RNA fractionation and via inhibition of in vitro aminoacylation. RESULTS: Serum from 1 patient with DM and interstitial lung disease immunoprecipitated glycyl-tRNA synthase along with only 1 of 4 associated tRNAs, in comparison with control anti-glycyl-tRNA synthetase antibodies, which bound the enzyme along with all 4 associated tRNAs. Immunoblotting findings and a lack of in vitro inhibition aminoacylation of tRNA(gly) by serum from this patient also suggested differences between the epitope specificity of this serum and that of other sera with anti-glycyl-tRNA synthetase antibodies. CONCLUSION: This identification of antibodies to glycyl-tRNA synthetase from a patient with DM underscores the association of this specificity with the disease. The finding that these antibodies bound an epitope outside the active site of the synthetase enzyme, in contrast to most anti-aminoacyl-tRNA synthetases, emphasizes the immunologic heterogeneity of these autoantibodies.

Antibody Specificity↗

Autoimmunity to RNA polymerase II is focused at the carboxyl terminal domain of the large subunit.

OBJECTIVE: Previous studies have demonstrated antibodies to the large (220 kd) polypeptide subunit of RNA polymerase II (Pol II) in sera from certain patients with scleroderma. In the present study, we sought to identify the autoantigenic region on this polypeptide. METHODS: A recombinant fusion protein, corresponding to the 52-heptapeptide repeat found in the carboxyl terminal domain (CTD) of the large Pol II subunit, was used to identify 15 patient sera that contained autoantibodies. Synthetic peptides CTD7 (representing a single heptapeptide) and CTD18 (representing 2 1/2 heptapeptide repeats) were used in a competitive inhibition assay to define the specificity of these sera and the importance of the CTD as an autoantigen. RESULTS: All 15 sera immunoprecipitated the Pol II subunit from radiolabeled cell extracts, and 11 of them bound the CTD fusion protein in immunoblots. Immunoprecipitation of Pol II was completely inhibited by CTD18 in 5 sera and partially inhibited in 4 additional sera. CONCLUSION: These results indicate that the CTD heptapeptide repeat is a focal point for autoimmune responses in scleroderma. It is likely that the repetitive sequence and high content of charged residues of this structure contribute to its role as an autoantigen.

Adult↗

The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells.

The effect of insulin-like growth factor-I on amino acid transport was studied by measuring the uptake of tritiated L-proline in the cultured human osteoblast-like SaOS-2 cells. The uptake of L-proline was supported by both transport system A, ASC and Gly and by Na+-dependent amino acid transport system A, and by Na+-independent system L. The initial rate of total L-proline uptake as a function of concentration showed saturation and obeyed Michaelis-Menten kinetics with Michaelis constant (Km) and maximum velocity (Vmax) values of 1.87 mM and 8.89 nmol x (mg protein)-1 x (3 min)-1, respectively. Na+-dependent L-proline uptake was significantly stimulated by insulin-like growth factor-I in a time- and concentration-dependent manner. Kinetic analysis showed that insulin-like growth factor-I enhanced transport activity by increasing the Vmax of transport without significant changes in the affinity (Km) of the carrier for the substrate. The increase in transport activity was significantly reduced by cycloheximide. The stimulated increment above basal L-proline uptake was completely inhibited by alpha-(methylamino) isobutyric acid, suggesting that only system A was affected by insulin-like growth factor-I. Na+-dependent L-proline uptake was also stimulated by insulin-like growth factor-II and insulin-like growth factor-I analogues. The insulin-like growth factor-I-stimulated L-proline uptake was inhibited by one of its binding protein, insulin-like growth factor binding protein-4, in a concentration-dependent manner.

Amino Acids↗

Long-term probucol treatment results in regression of xanthomas, but in progression of coronary atherosclerosis in a heterozygous patient with familial hypercholesterolemia.

A 66-year-old male heterozygous familial hypercholesterolemia (FH) patient with significant coronary atherosclerosis has been treated by us with probucol (1000 mg daily) for eight years. This treatment has produced significant reductions in the cholesterol levels of his serum, low density lipoprotein (LDL), and high density lipoprotein (HDL) from 237 +/- 20 mg/dl (mean +/- S.D.) to 156 +/- 15, from 175 +/- 8 to 111 +/- 16 mg/dl, and from 23 +/- 4 to 19 +/- 2 mg/dl, respectively. These reductions have been maintained for eight years. Serum triglyceride levels also decreased, from 220 +/- 54 to 146 +/- 36 md/dl. During this period, marked regression of xanthomas on the eyelids and finger extensor tendons was observed, while thickness of the Achilles tendons was reduced from 21.0 mm to 13.0 mm. On other hand, effort-induced anginal symptoms requiring additional antianginal medication have been noticed, and angiographically-demonstrated coronary atherosclerosis has progressed significantly during these eight years. These observations lead us to suggest that maintaining low levels of HDL cholesterol with probucol, even though resulting in satisfactory reduction of LDL cholesterol and marked regression of xanthomas, appears to be associated with the progression of atherosclerosis in the coronary arteries.

Aged↗

Glycosides of megastigmane and of the simple alcohols from Alangium premnifolium.

From the water-soluble fraction of a methanol extract of leaves of Alangium premnifolium, two new megastigmane glycosides, alangionosides N and O, along with three known megastigmane glycosides, dendranthemoside A and alangionosides A and B, were isolated. Shimaurinosides A and B, xylopyranosyl(1-->6)glucopyranosides of simple alcohols were also found to be constituents of the water-soluble fraction. Structures were determined by spectroscopic analyses.

Alcohols↗

In vitro and in vivo biological activities of a novel nonpolyglutamable anti-folate, MX-68.

MX-68 is a newly synthesized anti-folate, chemically designed not to undergo intracellular polyglutamation and to have increased affinity to dihydrofolate reductase (DHFR). In the present study, we examined the in vitro and in vivo biological activities of MX-68 compared with methotrexate (MTX) which forms several polyglutamates intracellularly. MX-68 dose-dependently inhibited the proliferation of PHA-, anti-CD3-, or PMA plus ionomycin-stimulated peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) from normal subjects as well as IL-1 beta- or TNF alpha-stimulated synovial fibroblastic cells (SC) from rheumatoid arthritis (RA) patients. Coaddition of folinic acid completely reversed the anti-proliferative effects of both MX-68 and MTX. Although the anti-proliferative activities of MX-68 were almost comparable to those of MTX, the washout study clearly showed the characteristic nature of MX-68. When drugs were removed during culture, the suppressive effect of MX-68 completely disappeared, whereas suppression by MTX was merely weakened. MX-68 dramatically suppressed the onset of collagen-induced arthritis (CIA) in mice when the drug was orally administered three times a week. starting from the day of first immunization. In this model, 2 mg/kg of MX-68 was sufficient to completely suppress arthritis, whereas suppression by the same dose of MTX was partial. These lines of evidence suggest that polyglutamation is not always a prerequisite in the anti-rheumatic effects of anti-folate. In addition, since intracellular accumulation of polyglutamates is thought to have adverse effects, MX-68 may become a more potent and less toxic anti-rheumatic drug than MTX.

2-Aminoadipic Acid↗