PubMed Health⌕ Search

Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 325 records · Page 18Linked to original sources

[A case of systemic lupus erythematosus associated with minimal change nephrotic syndrome].

A case of systemic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) in a 25-year-old female is described. The patient suddenly manifested butterfly rash and proteinuria was first pointed out on March, 1994. On admission, her skin biopsy indicated SLE. Subsequently, she developed nephrotic syndrome. Urinalysis showed heavy proteinuria (4.1 g/day), with no other abnormalities in the urinary sediment. Immunological examination revealed positive antinuclear antibody at a titer of 1:80 with a speckled pattern. Anti-ssDNA and anti-SS-A antibodies were positive, but other antibodies were negative. Serum complement (CH50) was within the normal range (30.5 U/ml). The renal biopsy showed no apparent cellular proliferation or increase of extracellular matrices in glomeruli by light microscopy. Slight deposition of IgG, IgM, C3 and C1q was focally seen in the mesangium and capillary wall by immunofluorescence. Electron microscopic examination revealed small and scattered dense deposits in the mesangium, subepithelium and subendothelium, associated with diffuse fusion of the foot processes of epithelial cells along the glomerular basement membrane. According to the WHO classification, the histological features were compatible with those of lupus nephritis (LN), class Ib. The patient was treated with PREDNISOLONE, Mizorbine and Dilazep, resulting in the disappearance of proteinuria and a normal serum level of total protein. The association of LN and MCNS is very rare. We also investigated the relationship between the intensity of proteinuria and histological types of 53 cases with LN examined in our laboratory. The cases with heavy proteinuria were mostly classified as WHO-Class IV and Class V. We report here a case of LN associated with MCNS and also review the literatures.

Adult↗

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗

Age-associated changes in the template-reading fidelity of DNA polymerase alpha from regenerating rat liver.

DNA polymerases (deoxynucleosidetriphosphate: DNA deoxynucleotidyltransferase EC 2.7.7.7.) were extracted from regenerating livers from young and aged rats. DNA polymerase alpha was separated and partially purified by DEAE-cellulose column chromatography, polyethyleneglycol precipitation, and phosphocellulose column chromatography, and fidelity levels were then monitored with the synthetic template-primer poly (dG-dC). The fidelity level of the DNA polymerase from regenerating liver a 4-month-old rat was very high, while that of the DNA polymerase from a 24-month-old rat was significantly decreased. To confirm this result, DNA was synthesized on poly (dG-dC) in a reaction mixture containing [32P]dTTP, and the synthetic polynucleotide was purified and digested with HhaI restriction endonuclease. After hydrolysis, the oligonucleotides were developed by two dimensional thin layer chromatography on PEI cellulose plates. Spots containing [32P]dTMP were observed when DNA polymerase from a 24 month-old rat was used, but none was found in polynucleotides synthesized using DNA polymerase from a 4 month-old rat. Nearest neighbor analysis suggested that dG-dT and dC-dT pairs were constructed by mis-incorporation due to DNA polymerase alpha.

Aging↗

Age-related changes in proliferating cell nuclear antigen levels.

To clarify the effect of aging on rat liver regeneration, we compared proliferating cell nuclear antigen (PCNA) levels in control and regenerating livers from young and aged rats 48 h after partial hepatectomy. The nucleoplasm and cytoplasm from regenerating livers of 2-month and 24 month-old rats were fractionated by phosphocellulose column chromatography, aliquots of fractions were transferred to nitrocellulose filters and the amounts of PCNA in each fraction were measured by an immunostaining method. Two forms of PCNA, L type (eluted at low concentrations of KC1) and H type (eluted at high KC1 concentrations) were observed in the nucleoplasm from both control and regenerating young rat liver. On the other hand, the cytoplasm contained P type (eluted in the pass-through fraction), L type and H type PCNA. In control liver from aged rats, three types of PCNA in the cytoplasm and two types in the nucleoplasm were present at decreased levels. In regenerating liver from young rats, the increases in L type in the cytoplasm and H type in the nucleoplasm were remarkable. However, none of the three PCNA types increased significantly during liver regeneration in aged rats. Treatment with DNase resulted in the disappearance of the H type with a concomitant increase in the P and L types. These results suggest that the H type is a complex form consisting of the P and L types of PCNA and DNA. These results suggest that the increase in the L type in the cytoplasm reflects newly synthesized PCNA production for cellular proliferation and that the increase in the H type in the nucleoplasm is a reflection of binding to DNA and the fundamental role of PCNA itself in liver regeneration in young rats. On the other hand, there was little increase in any of the three types in regenerating liver from 24-month-old rats. Thus, PCNA content may be closely related to the decrease in the rate of cellular proliferation in aged animals.

Aging↗

Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9.

We report a novel human gene whose product specifically associates with the negative regulatory domain of the Wilms' tumor gene product (WT1) in a yeast two-hybrid screen and with WT1 in immunoprecipitation and glutathione S-transferase (GST) capture assays. The gene encodes a 17-kDa protein that has 56% amino acid sequence identity with yeast ubiquitin-conjugating enzyme (yUBC) 9, a protein required for cell cycle progression in yeast, and significant identity with other subfamilies of ubiquitin-conjugating enzymes. The human gene fully complements yeast that have a temperature-sensitive yUBC9 gene mutation to fully restore normal growth, indicating that we have cloned a functionally conserved human (h) homolog of yUBC9. Transcripts of hUBC9 of 4.4 kilobases (kb), 2.8 kb, and 1.3 kb were found in all human tissues tested. A single copy of the hUBC9 gene was found and localized to human chromosome 16p13.3. We conclude that hUBC9 retains striking structural and functional conservation with yUBC9 and suggest a possible link of the ubiquitin/proteosome proteolytic pathway and the WT1 transcriptional repressor system.

Amino Acid Sequence↗

Detection of aneuploidy in interphase nuclei from non-small cell lung carcinomas by fluorescence in situ hybridization using chromosome-specific repetitive DNA probes.

Interphase fluorescence in situ hybridization (FISH) is particularly useful for detecting chromosome changes in tumors exhibiting a low mitotic index, as is the case in many human non-small cell lung carcinomas (NSCLCs). A panel of centromeric DNA probes specific for the autosomes 6, 7, 8, 9, 12, 17, and 18 was used to analyze 17 primary NSCLCs. Evidence for aneuploidy was obtained in all specimens. Gain of part or all of chromosome 7 was especially prominent, occurring in a large population of cells in each of 14 tumors (82%). Extra centromeric copies of chromosomes 6, 12, and 17 were also common, being observed in 9 to 11 cases each. Gain of chromosome 9 was infrequent (three tumors). In two cases, most of the nuclei had only a single chromosome 9 fluorescent signal. Karyotypic findings were available for six cases and were generally consistent with the FISH data. Both methods revealed considerable heterogeneity within individual tumors. NSCLC specimens from 26 males were assayed with a Y-specific centromeric sequence; loss of the Y was observed in 13 cases (50%). These investigations demonstrate the feasibility of interphase FISH for the successful analysis of numerical chromosome changes in NSCLCs.

Aneuploidy↗

Occurrence and structural analysis of highly sulfated multiantennary N-linked glycan chains derived from a fertilization-associated carbohydrate-rich glycoprotein in unfertilized eggs of Tribolodon hakonensis.

This study represents the first detailed investigation of the nature of highly sulfated (keratan-sulfate-like) complex-type asparagine-linked glycans having a tetraantennary core structure and shows the effectiveness of fast-atom-bombardment mass spectrometric (FAB-MS) methods incorporating derivatization and mild methanolysis for analyzing such complex types of sulfated glycans. The structure of the N-glycan chains was unambiguously established by a combination of compositional analysis, methylation analysis, mild methanolysis for desulfation, hydrazinolysis/nitrous acid deamination, enzymatic (endo-beta-galactosidase and peptide:N-glycosidase F) digestions, and instrumental analyses (1H-NMR spectroscopy and FAB-MS) which revealed the novel repeating sulfated carbohydrate sequences, +/- Gal beta 1-->4Gal beta 1[-->(HSO3-->6)GlcNAc beta 1-->3(+/- Gal beta 1-->4)Gal beta 1]n--> (see Structure I; p + q + r + s approximately 14). This sequence is unique in: (a) the skeletal structure is similar to that of keratan sulfate but is completely devoid of 6-O-sulfated Gal residues and (b) the presence of branched Gal residues in the sequence -->4GlcNAc beta 1-->3(Gal beta 1-->4)Gal beta 1-->. [formula: see text]

Animals↗

Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome 7, 7q36.

A Ras-related GTP-binding protein cDNA has been isolated from a human skin fibroblast cDNA library using a genomic subclone derived from a YAC clone as a probe. The polypeptide, consisting of 184 amino acids deduced from nucleotide sequences, contains five repeats of the Ras-related GTP-binding region and is highly homologous to the rat RHEB (Ras homologue enriched in brain) gene, which encodes a Ras-related growth factor- and synaptic activity-regulated protein, with 98.9% amino acid identity. Therefore, it is suggested to be a human homologue of the rat RHEB protein, and we have designated it human RHEB. Using fluorescence in situ hybridization, we concluded that this human RHEB gene was localized to band q36 on chromosome 7. Considering the chromosomal localization as well as the potential function of this protein, it will be very important to investigate whether it may play a role in the etiopathogenesis of holoprosencephaly type 3 or hereditary sacral agenesis, in which the disease susceptible locus is linked to the microsatellite marker, D7S22, in this chromosomal region, 7q36.

Amino Acid Sequence↗

Cloning of a putative ligand for the T1/ST2 receptor.

T1/ST2 is a receptor-like molecule homologous to the type I interleukin-1 receptor. Despite this sequence similarity, we have been unable to demonstrate binding of T1/ST2 to any of the three interleukin-1 species. In searching for a ligand for T1/ST2, we have cloned a cell surface protein to which it binds. This protein is unable to initiate signal transduction by the T1/ST2 receptor in several in vitro assays.

3T3 Cells↗

Two modes of activity-dependent synaptogenesis of cerebral neurons in vitro.

Effects of transduction activity and transmission activity on synaptogenesis of chick cerebral neurones in dissociated cell culture were studied electrophysiologically using two blockers for these activities, tetrodotoxin (TTX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. CNQX inhibited the increase of evoked EPSCs more effectively than TTX, whereas both blockers similarly reduced the increase of miniature EPSCs (Minis). These data indicated that not only transduction-dependent transmission activity but also transduction-independent spontaneous activity regulate the synaptic efficiency. These two activities are suggested to change the quantal amplitude and the number of synaptic sites, respectively.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Neuronal and muscular functions as parameters of graft viability in small bowel transplantation.

The physiological properties of neurons and smooth muscles were studied after cold preservation of a rat small intestinal graft, in order to evaluate the graft viability before reperfusion. A 25-cm jejunal graft was harvested from a Lewis rat and stored in University of Wisconsin solution for 0, 12, 24, 48, and 72 hr at 4 degrees C (n = 8, each group). The intestinal samples were physiologically studied at the end of cold preservation. The positive rates of the specimens showing both biphasic nervous activities and spontaneous rhythmic activities were 100, 100, 88, 25, and 0% in 0-, 12-, 48-, and 72-hr preservation groups, respectively. The maximal contractions produced by acethylcholine chloride were 1.12 +/- 0.32, 0.63 +/- 0.22, 0.43 +/- 0.15, 0.52 +/- 0.32, and 0.27 +/- 0.13g for the 0-, 12-, 24-, 48-, and 72-hr preservation groups, respectively. The graft survivals after syngeneic transplantation (n = 6, each group) were 6 out of 6 (100%), 5 out of 6 (83%), 5 out of 6 (83%), 1 out of 6 (17%), and 0 out of 6 (0%) for the 0-, 12-, 24-, 48-, and 72-hr preservation groups, respectively. The graft survival correlated closely with the positive sample rates of the specimens, showing both biphasic nervous activities and spontaneous rhythmic activities. It only took about 1 hr and 20 min to complete the physiological examination of the graft, and thus, such an examination of the graft is considered to be both a simple and a reliable method for predicting graft viability before transplantation.

Animals↗

Okadaic acid gives concentration-dependent reciprocal effects on the fluid phase endocytosis activated by Ca2+ and phorbol 12-myristate 13-acetate.

Incubation of a human fibrosarcoma cell line HT-1080 in increasing concentration of Ca2+ was found to enhance endocytic internalization of a fluid phase marker, horseradish peroxidase. At 16.8 mM Ca2+, generation of the effect required incubation for more than 45 min. The effect was reversed by removal of the excess ion for 30 min. Monitoring the intracellular concentration showed that the incubation induced a transient large Ca2+ influx followed by a recovery to 230 +/- 50 nM instead of the normal level of 83 +/- 5 nM. The activation was not inhibited by inhibitors of protein kinases nor a cAMP antagonist. In contrast, the effect was prevented by okadaic acid (OKA) at 100 nM without detectable effect on the basal activity. Fluid phase uptake by HT-1080 cells was also enhanced by phorbol 12-myristate 13-acetate (PMA). In contrast to the case with Ca2+, OKA at 100 nM did not prevent the PMA effect but further enhanced the endocytosis. The effect of OKA was concentration-dependent, as the reagent at 1 microM inhibited not only both the activation but also the basal activity. In Ca(2+)- or PMA-stimulated cells, FITC-dextran was delivered to endosomes that had been labeled with TRITC-transferrin. In contrast, following treatment with a combination of PMA and 100 mM OKA, fluid phase was internalized in vesicular compartments devoid of transferrin labeling. These results suggest that, through differential modifications of protein phosphorylation, endocytosis can be enhanced distinctively either by employing conventional receptor-bearing compartments or generating a new endosomal population.

Biological Transport↗

A randomized trial comparing ftorafur alone with ftorafur plus tamoxifen in postoperative adjuvant therapy for breast cancer. Kinki Area Research Group for Postoperative Adjuvant Therapy for Breast Cancer.

A randomized study was performed in 35 centers in the Kinki area of Japan to determine the effectiveness of ftrorafur (FT) plus tamoxifen (TAM) compared with FT monotherapy in postoperative adjuvant therapy for breast cancer. Patients were randomized by the envelope method to receive either FT 600 mg/day or FT 600 mg/day plus TAM 20 mg/day orally for 1 year, starting on day 7 after mastectomy. Between April 1982 and January 1985, 628 patients were assigned to treatment with FT alone and 626 to treatment with FT + TAM. Of these, 571 (90.9%) and 539 (86.1%) patients, respectively, met the eligibility requirements for this study. There were no significant differences in major background factors between the two groups of eligible patients. Five-year survival rates were 91.4% for FT alone and 91.1% for FT+TAM (not significantly different). Five-year disease-free survival rates showed a tendency towards a better prognosis (P = 0.090) in the FT + TAM group, with observed rates of 83.0% for FT alone and 86.7% for FT + TAM. Stratified analysis showed that disease-free survival with FT + TAM is better than with FT alone for patients aged 50 years or more ( P = 0.048) and for patients with from one to three positive nodes (P = 0.064).

Adult↗