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Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 487 records · Page 27Linked to original sources
PubMed1999

Analysis of elastin metabolism in patients with late-onset focal dermal elastosis.

Late-onset focal dermal elastosis has recently been described as new clinical entity characterized by pseudoxanthoma elasticum-like eruptions and an accumulation of normal-appearing elastic fibres in the dermis. Elastin and collagen contents of the skin of 2 patients were 2- and 1.4-fold higher than in the skin of controls, respectively. A focal accumulation of elastin but not of fibrillin-1 was observed by immunohistochemical staining. The levels of type I and III collagen and elastin mRNAs isolated from cultured patient fibroblasts were elevated 2-3-fold compared with control fibroblasts. There was no significant change in the excretion of elastin peptides in the urine of patients and controls. These results suggest that the focal accumulation of elastic fibres in the patient skin may be related to overexpression of elastin rather than to altered degradation of elastin.

Age of Onset↗
PubMed1999

Prognostic significance of the PC10 index for patients with stage II and III oesophageal cancer treated with radiotherapy.

The monoclonal antibody PC10 is used for immunohistochemical staining of the proliferating cell nuclear antigen (PCNA). The percentage of PC10-positive cancer cells is defined as the PC10 index. We evaluated the relationship between the PC10 index in pretreatment endoscopic biopsies and the prognoses of 47 patients with Stage II-III oesophageal squamous cell carcinoma treated with radiotherapy. The patients with a PC10 index > 40% had significantly poorer prognoses than the other patients (p = 0.0007). Proportional hazards model analysis indicated that only the PC10 index was a prognostic factor (p = 0.0009). The patient group of complete responders showed significantly lower PC10 indices compared to patients with a partial response or no change (p = 0.049). The PC10 index can be a good predictive indicator of the prognosis in patients with Stage II-III oesophageal cancer treated with radiotherapy.

Aged↗
PubMed1999

Involvement of interleukin-18 (IL-18) in mixed lymphocyte reactions (MLR).

The in vitro mixed lymphocyte reaction (MLR) is a useful model to study alloresponsiveness to histocompatibility antigens. Secretion of different cytokine proteins in the supernatant of allo-MLR cultures has been reported in a few studies. We studied the levels of the cytokines interferon gamma (IFN-gamma) and interleukin-6 (IL-6), IL-10, IL-12, and IL-18 in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-y, IL-6, IL-10, and IL-18 were detected at 12 h after MLR and markedly increased thereafter. In contrast, secretion of IL-12 was detected after 48-72 h. These results suggested that IFN-gamma production depended on IL-18 in the early phase of MLR and depended on both IL-18 and IL-12 in the late phase. An antibody (Ab) neutralizing test was also performed. The levels of IFN-gamma were significantly downregulated after the addition of anti-IL-18 Ab, anti-IL-12 Ab, or anti-IFN-y Ab, and the levels of IL-12 were significantly downregulated after the addition of anti-IL-12 Ab and anti-IL-18 Ab. Treatment with these Ab did not suppress IL-6 production at all. The two-way MLR showed the same tendency as the one-way MLR. These results suggest the importance of IL-18 and IL-12 in allogeneic cell interactions and also suggest the usefullness of these Ab as regulators of alloresponsiveness.

Culture Media↗
PubMed1999

Development of Graves' hyperthyroidism from primary hypothyroidism in a case of thyroid hemiagenesis.

We report a 42-year-old female with right thyroid hemiagenesis who initially presented with hypothyroidism and then developed hyperthyroidism. The serum titer of thyroid-stimulating antibody was weakly positive in the initial hypothyroid state, and then markedly increased along with the development of hyperthyroidism, while thyroid stimulation-blocking antibody was continuously negative throughout the observation period. Thyroid histology of biopsied specimens during the hypothyroid state demonstrated diffuse thyroiditis with mononuclear cell infiltrations; however, the histology during the hyperthyroid state showed hyperplasia in follicular epithelial cells accompanied by partial lymphocyte infiltration. This is the first case of thyroid hemiagenesis associated with a conversion from primary hypothyroidism due to Hashimoto's thyroiditis to hyperthyroidism due to Graves' disease.

Adult↗
PubMed1999

Multiple primary cancers of the esophagus and thyroid gland.

The occurrence of multiple primary cancers in the aerodigestive tract is a well known phenomenon that has been explained by the concept of 'field carcinogenesis'. Metachronous or synchronous esophageal cancer has usually been identified in patients with head and neck cancer, gastric cancer or colon cancer. The incidence of multiple primary cancers of the esophagus and thyroid gland is very low. We treated four patients with synchronous cancers of the cervical esophagus and the thyroid gland. Histologically, all of the esophageal cancers were squamous cell carcinomas. Thyroid cancers were evaluated as papillary carcinoma or follicular carcinoma. Both the esophageal cancer and the thyroid cancer frequently metastasized to lymph nodes. All patients had multiple lymph nodes metastasis from the esophageal or the thyroid cancer. In one patient, both the esophageal and the thyroid cancers were detected in the same lymph node. Three of four patients died from recurrence of esophageal cancer. The prognosis of these patients was poor. In the treatment of esophageal carcinoma, cancers of other organs including the thyroid gland should be carefully investigated.

Aged↗
PubMed1999

Multiple liver metastases of breast cancer: report of a case successfully treated with hormone-cytokine-chemotherapy.

The prognosis of patients with hepatic metastasis from breast cancer is usually extremely poor. We present the case of a 39-year-old Japanese woman diagnosed with multiple liver metastasis from breast cancer. A novel approach consisting of hormone-cytokine-chemotherapy with an arterial infusion therapy was carried out. Computed tomography and ultrasonography revealed that the multiple liver metastases were reduced with remaining calcification. Tumor markers decreased rapidly. Complete regression was achieved after these treatments. To date, there has been no relapse during the 8-year follow-up period. These results suggest that the hormone-cytokine-chemotherapy might be a rational modality of treatment against multiple metastatic breast cancer.

Adult↗
PubMed1999

Evaluation of the mouse lymphoma tk assay (microwell method) as an alternative to the in vitro chromosomal aberration test.

In order to evaluate the utility of the mouse lymphoma assay (MLA) for detecting in vitro clastogens and spindle poisons and to compare it with the in vitro chromosomal aberration test (CA), we conducted an international collaborative study of the MLA that included 45 Japanese laboratories and seven overseas laboratories under the cooperation of the Ministry of Health and Welfare of Japan and the Japanese Pharmaceutical Manufacturer's Association. We examined 40 chemicals; 33 were reportedly positive in the CA but negative in the bacterial reverse mutation assay, six were negative in both assays and one was positive in both. We assayed mutations of the thymidine kinase (TK) locus (tk) of L5178Y tk +/- mouse lymphoma cells using the microwell method. According to our standard protocol, cells were exposed to the chemical for 3 h, cultured for 2 days and TK-deficient mutants were expressed in 96-well plates under trifluorothymidine. Each chemical was coded and tested by two or three laboratories. Among the 34 CA-positive chemicals, positive MLA results were obtained for 20 and negative results were obtained for nine. The remaining five chemicals were inconclusive or equivocal because of discrepant inter-laboratory results or reproduced discrepant results, respectively. Among the six CA-negative chemicals, one was negative in the MLA, two were positive and three were inconclusive. Thus, the MLA could detect only 59% (20/34) of CA-positive chemicals. We concluded that the MLA was not as sensitive as the CA. Some MLA-negative chemicals evoked positive responses in the CA only after long continuous treatment. These might also be genotoxic in the MLA with long continuous treatment. Improvement of the MLA protocol, including alteration of the duration of the treatment, might render the MLA as sensitive as the CA.

Animals↗
PubMed1999

Genome structure of Ri plasmid (2). Sequencing analysis of T-DNA and its flanking regions of pRi1724 in Japanese Agrobacterium rhizogenes.

We sequenced 42.6 kb including T-DNA and its flanking regions which corresponds to about 1/5 of entire length of a mikimopine-type Ri plasmid, pRi1724 in A. rhizogenes. We identified 37 ORFs (Open Reading Frames) including genes in total. Among them, 20 ORFs are probably new genes. Those ORFs have similarity with those in Agrobacterium and 9 ORFs of them was newly found on Ri plasmids.

DNA, Bacterial↗
PubMed1999

Mutational analysis of the reactive site loop of Streptomyces metalloproteinase inhibitor, SMPI.

Streptomyces metalloproteinase inhibitor (SMPI) is the only inhibitor to show "standard mechanism inhibition" against metalloproteinases. SMPI is a globular protein with an exposed loop containing the reactive site, C64-V65. To analyze the importance of basic residues in the reactive site loop of SMPI, mutants were constructed for R60, K61, and R66 (R60A, K61A, R66A, R60/K61A, 60/61/66A, and 60/61/66E). The mutants involving only R60, K61, and R60/K61 residues, respectively, showed strong inhibitory activity and were stable against enzyme activity. Both the triple mutants showed very weak inhibitory activity and underwent rapid degradation. The addition of basic residues to the loop (V62R and T63R) did not cause any further increase in inhibitory activity. These results suggest that basic residues in the reactive site loop play some role in maintaining a stable enzyme-inhibitor complex. The R66 mutant showed reduced activity and was rapidly degraded by enzymes. It was concluded that R66 is essential for maintaining a strong hydrophobic interaction with the S1' hydrophobic pocket of the enzyme. To investigate the roles of the disulfide bridge and the P68 residue near the reactive site, C64/69S and P68T mutants were constructed. These mutants showed very weak inhibitory activity and were rapidly degraded by enzymes. These results suggest that the disulfide bridge and P68 residue are very essential for SMPI to function as an inhibitor.

Bacterial Proteins↗
PubMed1999

Crystal structure of prolyl aminopeptidase from Serratia marcescens.

Prolyl aminopeptidase from Serratia marcescens specifically catalyzes the removal of N-terminal proline residues from peptides. We have solved its three-dimensional structure at 2.3 A resolution by the multiple isomorphous replacement method. The enzyme consists of two contiguous domains. The larger domain shows the general topology of the alpha/beta hydrolase fold, with a central eight-stranded beta-sheet and six helices. The smaller domain consists of six helices. The catalytic triad (Ser113, His296, and Asp268) is located near the large cavity at the interface between the two domains. Cys271, which is sensitive to SH reagents, is located near the catalytic residues, in spite of the fact that the enzyme is a serine peptidase. The specific residues which make up the hydrophobic pocket line the smaller domain, and the specificity of the exo-type enzyme originates from this smaller domain, which blocks the N-terminal of P1 proline.

Aminopeptidases↗
PubMed1999

Prevalence of maternal cytomegalovirus (CMV) antibody and detection of CMV DNA in amniotic fluid.

The prevalence of cytomegalovirus (CMV) IgG antibody was determined in 573 pregnant women in the first trimester. The overall prevalence of CMV IgG antibody was 77.5%. The rate of seropositivity was 67.7% in women < 25 yr, and increased with age to 85.7% in women 40 yr. These results imply that young women in Japan are at increased risk for primary CMV infection during pregnancy and that congenital CMV infection rates might increase in the future. We conducted a prospective study of 75 pregnant women who underwent amniocentesis for various indications to determine if CMV DNA could be detected in the amniotic fluid. None had symptoms associated with CMV infection, CMV IgM antibody, or seroconversion to CMV IgG antibody during pregnancy. CMV DNA was not detected in the amniotic fluid using a polymerase chain reaction assay. The 65 fetuses, including 3 sets of twins, were followed through birth. CMV DNA was not detected in urine samples obtained within the first 2 weeks of life. In conclusion, CMV DNA was not detected in the amniotic fluid of women who did not have CMV infection. These results, however, suggest that the negative predictive value of prenatal amniotic fluid analysis is high and that the presence of CMV DNA in the amniotic fluid has clinical significance for the diagnosis of congenital CMV infection if detected in pregnant women.

Adult↗
PubMed1999

Effect of 5-fluorouracil on cell cycle regulatory proteins in human colon cancer cell line.

We investigated the effects of 5-fluorouracil (5-FU) on cell cycle-regulating proteins in RPMI 4788 cells. 5-FU inhibited cell growth dose-dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short-term treatment (3 or 24 h) with 5-FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A-associated kinase activity assay showed that cyclin A-cyclin-dependent kinase (Cdk) 2 kinase activity was altered by 5-FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5-FU treatment was observed in three other human cancer cell lines, DLD-1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5-FU, and the cyclin A function and degradation mechanism remain normal.

Antimetabolites, Antineoplastic↗
PubMed1999

Serum des-gamma-carboxy prothrombin levels determined by a new generation of sensitive immunoassays in patients with small-sized hepatocellular carcinoma.

OBJECTIVE: Des-gamma-carboxy prothrombin (DCP), also called protein induced by vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available immunoassays for DCP are not sensitive enough to detect HCC at an early stage. Recently, two new immunoassays with enhanced sensitivity were developed. The aim of this study was to assess the diagnostic values of the new methods in patients with small-sized HCC. METHODS: Coded serum samples obtained from 36 patients with small-sized and single-nodular HCC (< or = 3 cm in diameter) and 49 patients with posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were determined in three different ways: 1) conventional EIA; 2) a new immunoassay using the electrochemiluminescence (ECLIA) detection system; and 3) a new immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were also determined. RESULTS: In 36 patients with small-sized HCC, the rates of abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%, 27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%. CONCLUSIONS: Compared with the conventional method, the sensitivity in detecting small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA). The overall performance as evaluated by an ROC analysis was significantly better in ECLIA than in IRMA.

Biomarkers↗
PubMed1999

Blinded, prospective, and serial evaluation by quantitative-EEG in interferon-alpha-treated hepatitis-C.

OBJECTIVES: To estimate the effect of brain function due to IFN-alpha in chronic hepatitis C patients by the quantitative EEG. METHODS: 56 chronic hepatitis C patients were administered IFN-alpha intramuscularly at 9x10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained in each subject before, at 2 and 4 weeks, and after completing the treatment. Resting EEG without artifacts was selected for quantitative EEG analysis, which was performed blindly. The frequency range was divided into delta to beta. The absolute and relative powers of each frequency band in each subject were calculated and the differences of these powers at different stages were analyzed statistically. RESULTS: The absolute powers of slow waves (delta, theta 1, and theta 2) increased while alpha 2 and fast wave (beta) decreased significantly at all locations during IFN-alpha administration. The total power and alpha 1 values revealed no significant alterations. The relative power revealed the same alteration during treatment. These changes disappeared following the treatment. Such diffuse slowing in the EEG was revealed by the total change in the whole subjects. CONCLUSIONS: Diffuse slowing in the EEG was induced by IFN-alpha, was reversible, and was evident as the total change in the subjects. These findings suggested mild IFN-alpha-induced encephalopathy.

Analysis of Variance↗
PubMed1999

Cell surface galactosylation is essential for nonsexual flocculation in Schizosaccharomyces pombe.

We have isolated fission yeast mutants that constitutively flocculate upon growth in liquid media. One of these mutants, the gsf1 mutant, was found to cause dominant, nonsexual, and calcium-dependent aggregation of cells into flocs. Its flocculation was inhibited by the addition of galactose but was not affected by the addition of mannose or glucose, unlike Saccharomyces cerevisiae FLO mutants. The gsf1 mutant coflocculated with Schizosaccharomyces pombe wild-type cells, while no coflocculation was found with galactose-deficient (gms1Delta) cells. Moreover, flocculation of the gsf1 mutant was also inhibited by addition of cell wall galactomannan from wild-type cells but not from gms1Delta cells. These results suggested that galactose residues in the cell wall glycoproteins may be receptors of gsf1-mediated flocculation, and therefore cell surface galactosylation is required for nonsexual flocculation in S. pombe.

Carbohydrates↗