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Biomedical subjects

M Asada

Publications and source records attributed to M Asada.

At least 73 records · Page 4Linked to original sources
PubMed1998

An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.

We detected in the brain and then cloned two novel, short forms of human and mouse fibroblast growth factor (FGF)-5 mRNA, which were designated human FGF-5S (hFGF-5S) and mouse FGF-5S (mFGF-5S), respectively. Genomic analysis indicated that mFGF-5S and authentic mFGF-5 mRNAs were transcribed from a single gene; hFGF-5S and mFGF-5S mRNAs were generated by excluding the second exon of the respective FGF-5 genes, and the alternatively spliced mRNAs encoded for 123- and 121-amino acid proteins, respectively. Indeed, a neuron-like cell line expressing mFGF-5S mRNA secreted a protein of the expected size and with FGF-5 antigenicity. In PC12 cells, expression of hFGF-5 or exposure to hFGF-5 protein induced differentiation. Neither expression of hFGF-5S, alone, nor co-expression of hFGF-5S with hFGF-5 induced significant differentiation. At high concentrations, hFGF-5S protein partially antagonized FGF-5 activity, whereas by itself, hFGF-5S exerted very weak neurotrophic activity. hFGF-5S protein binds to FGF receptor (FGFR)-1 on PC12 transfectants and partially inhibits hFGF-5-induced tyrosine phosphorylation of FGFR-1 and an FGFR substrate, but it also induces phosphorylation by itself. These results suggest that FGF-5S is a naturally expressed partial agonist/antagonist of FGF-5 neurotrophic activity in the brain and that its effects are exerted in part at the level of the receptor.

Alternative Splicing↗
PubMed1998

[A case of adenocarcinoma of the thymus].

We report an adenocarcinoma of the thymus in a 39-year-old male. The patient presented with chest pain, and the chest X-ray film and chest CT showed an abnormal mass in the mediastinum. A preoperative clinical diagnosis of invasive thymoma was suspected. The tumor was resected along with the pleura and pericardium. The pathological findings were compatible with those of adenocarcinoma of the thymus. Despite a thorough examination, no primary tumor could be found. An adenocarcinoma of the thymus is rare and to the authors knowledge there are few previous reports in the literature.

Adenocarcinoma↗
PubMed1998

Molecular characterization of phenylketonuria in Japanese patients.

We characterized phenylalanine hydroxylase (PAH) genotypes of Japanese patients with phenylketonuria (PKU) and hyperphenylalaninemia (HPA). PKU and HPA mutations in 41 Japanese patients were identified by denaturing gradient gel electrophoresis and direct sequencing, followed by restriction fragment length polymorphism analysis to find a large deletion involving exons 5 and 6. Of 82 mutant alleles, 76 (92%) were genotyped showing 21 mutations. The major mutations were R413P (30.5%), R243Q (7.3%), R241 C (7.3%), IVS4nt-1 (7.3%), T2781 (7.3%), E6nt-96A-->g (6.1%), Y356X (4.9%), R111X (3.7%), and 442-706delE5/6 (2.4%). Eight new mutations (L52 S, delS70, S70P, Y77X, IVS3nt-1, A132 V, W187 C, and C265Y) and a polymorphism of IVS10nt-14 were detected. In vitro PAH activities of mutant PAH cDNA constructs were determined by a COS cell expression system. Six mutations, viz., R408Q, L52 S, R241 C, S70P, V388 M, and R243Q, had 55%, 27%, 25%, 20%, 16% and 10% of the in vitro PAH activity of normal constructs, respectively. The mean pretreatment phenylalanine concentration (0.83+/-0.21 mmol/l) of patients carrying the R408Q, R241 C, or L52 S mutation and a null mutation was significantly lower (P<0.0005) than that (1.99+/-0.65 mmol/l) of patients with both alleles carrying mutations associated with a severe genotype. Simple linear regression analysis showed a correlation between pretreatment phenylalanine concentrations and predicted PAH activity in 29 Japanese PKU patients (y=31.9-1.03x, r=0.59, P<0.0001). Genotype determination is useful in the prediction of biochemical and clinical phenotypes in PKU and can be of particular help in managing patients with this disorder.

Animals↗
PubMed1998

p21Cip1/WAF1 is important for differentiation and survival of U937 cells.

Vitamin D3 (VD3) induces monocytic differentiation of U937 cells. Induction of p21Cip1/WAF1 (p21) and subsequent G0/G1 cell-cycle arrest are required in this process. Using a system of inducible expression of ectopic p21, we demonstrated the important role of p21 in the induction of monocytic differentiation in U937 cells. Prior induction of antisense-p21 expression significantly suppressed p21 expression, and resulted in inhibition of VD3-induced U937 differentiation. Moreover, induction of expression of antisense-p21 in VD3-differentiated U937 cells resulted in apoptosis of the cells. This was associated with activation of Cdc2 and caspase-3 like protease. Our results suggest that p21 is required for the initiation of the early steps of differentiation as well as survival of differentiated cells.

Apoptosis↗
PubMed1998

Effect of tylosin tartrate (Tylan Soluble) on cellular immune responses in chickens.

Although many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance immune function. Tylosin is a macrolide antibiotic approved for the control of mycoplasmosis in poultry. The purpose of this investigation was to determine the effect of tylosin on cellular immune functions in chickens. There was no significant difference in adherent splenocyte chemotaxis between tylosin-treated and untreated (control) chickens. Tylosin increased splenocyte proliferation and splenocyte conditioned medium (CM) proliferative activity above control levels. Removal of adherent splenocytes before preparation of CM caused a reduction in CM proliferative activity. Tylosin also increased antitumor activity of splenocytes. These data are the first to suggest that the macrolide antibiotic, tylosin tartrate, has a modulatory effect in chickens on the immune parameters studied.

Animals↗
PubMed1998

Effect of tylosin tartrate on humoral immune responses in chickens.

While many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance the immune function. Tylosin tartrate is a macrolide antibiotic approved for the control of mycoplasmosis in poultry. The purpose of this investigation was to determine the effect of tylosin on the humoral immune functions in chickens. Three days after oral tylosin tartrate administration, 4- or 8-week-old chickens were immunized intravenously with carbolic acid-killed Brucella abortus bacterin or sheep red blood cells. Seven days (plasma antibodies titre) or 4 days (antibody forming cells) post-immunization, there was a significant increase in antibody production as well as in the numbers of antibody-producing cells in tylosin tartrate-administered chickens compared with the untreated controls. However, 3 days after tylosin tartrate administration, there was no difference in the distribution of T-lymphocyte subpopulations (CD4 or CD8 positive cells) or B lymphocytes (surface immunoglobulin positive cells) in either the peripheral blood or spleens or untreated control chickens.

Animals↗
PubMed1998

Dynamics of QT interval in a patient with long QT syndrome and a normal QT interval.

A case report of a 15-year-old girl who experienced syncope and torsades de pointes is presented. The girl had a normal QT interval (QTc=0.37 sec) on the resting electrocardiogram (ECG). Infusion of isoproterenol induced QT prolongation (QTc=0.62 sec) and frequent occurrence of multiform ventricular premature beats. Her Holter ECG showed a prolongation of the QTc interval with a shortening of the RR interval. Low-frequency power (LF) and high-frequency power (HF) of heart rate variability were evaluated from the Holter ECG. The patient showed a statistically significant negative QTc/HF and a significant positive QTc/(LF/HF) relationship, whereas none of the age- and sex-matched healthy subjects showed these relationships. The slope of the QT/RR relationship for the patient was below the lower limit of the normal range. This report describes the unusual relationship of QT interval to RR interval and heart rate variability in a long QT syndrome patient with a normal QT interval on resting ECG.

Adolescent↗
PubMed1998

Subependymoma in the lateral ventricle incidentally detected by routine brain examination--case report.

A 42-year-old male visited our hospital for a routine brain examination, which incidentally identified an intraventricular mass lesion (2.7 x 1.6 x 1.2 cm3). Magnetic resonance imaging showed the tumor was isointense on the T1-weighted image and hyperintense on the T2-weighted and proton images. The intraventricular tumor was totally extirpated through the interhemispheric ipsilateral transcallosal approach. The histological diagnosis was subependymoma. Neuroimaging cannot differentiate this benign neoplasm from other more aggressive tumors. Widespread use of the medical checkup system is expected to find a higher incidence of otherwise non-identified asymptomatic lesions. Surgical extirpation is one of the treatment options to establish the correct diagnosis and to prevent symptoms.

Adult↗
PubMed1998

Continuous and simultaneous cultivation of benthic food diatom Nitzschia sp. and abalone Haliotis sieboldii by using deep seawater.

By using low-temperature, clean, and nutrient-rich properties of deep seawater (DSW; seawater below the euphotic layer), a continuous and simultaneous cultivation system for a benthic food diatom, Nitzschia sp., and juvenile abalone was established. Cell suspension of Nitzschia sp. was added to a bioreactor made of acrylic pipe (7 cm diameter x 50 cm long) containing short vinyl tubes (2 cm diameter x 2 cm long) as substrata. DSW collected from 320 m depth at Muroto City, in Kochi Prefecture, Japan, was supplied to the reactor and incubated under natural light (ca. 6000 lux) with a continuous DSW flow rate of 40 turnovers per hour. After growing enough benthic diatoms in the reactor, juveniles of abalone, Haliotis sieboldii (shell length ca. 10-20 mm) were put into a reactor, and cultivated simultaneously with food diatoms in the continuous flow system. During the four-month incubation, 7-month-old abalone juveniles with a shell length of 12.4 (average) +/-0.2 (SD) mm were grown to 19.4 (+/-1.7) mm in the reactor. Daily growth rates of abalones were 50-110 µm/day. These results indicate that the continuous cultivation system with DSW supports the growth of juvenile abalone without any supply of seaweed until it grows to release size.

Journal Article↗
PubMed1997

DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation.

Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues 286A, 133R, 282W, 132E, and 213ter were established from five independent Li-Fraumeni syndrome families. When cell cycle regulation in response to gamma-irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all cases except for 282W LCL, which showed a normal G1 checkpoint. On the other hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase 2 activity was defective in all these LCLs. The mitotic checkpoint was also defective in the two LCLs analyzed as either competent or incompetent for G1 arrest. When radiation-induced apoptosis, which requires wild-type p53 function under optimal conditions, was studied, all of these LCLs showed significant failure compared to normal LCLs. These findings indicate that although p53-dependent transactivation and G1-S-phase cell cycle control are variably dysregulated, the induction of apoptosis and control of the cell cycle at S-phase-G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families to cancer. Furthermore, the approach presented is a potentially useful method for studying individual carriers of different germ-line p53 mutations and different biological features.

Adolescent↗
PubMed1997

Increased expression of highly branched N-glycans at cell surface is correlated with the malignant phenotypes of mouse tumor cells.

Three NIH3T3 transformants, MTAg, MTPy, and MT1, which grow similarly in soft agar media, showed remarkable differences in athymic mice: MTAg grew more rapidly than MTPy, whereas MT1 and NIH3T3 did not, and only MTAg metastasized in lung. Structural analysis of N-glycans from plasma membrane glycoproteins revealed that each sample contains similar amounts of N-glycans, but the relative amounts of 2,6-branched tri- and tetra-antennary oligosaccharides prominently increase and the relative amounts of biantennary oligosaccharides prominently decrease in the order of NIH3T3, MT1, MTPy, and MTAg, whereas those of others remained constant. Western blot analysis revealed that binding of Datura stramonium agglutinin, which interacts with 2,6-branched tri- and tetra-antennary oligosaccharides, is significantly increased in several bands from MTAg compared with NIH3T3, two of which are tentatively identified as lysosome-associated membrane protein-1 and fibronectin (FN)-receptor. It was also shown that the spreading of MTAg on FN-coated plates is dramatically inhibited with the anti-FN-receptor antiserum when compared with NIH3T3. These results indicate that the increased expression of highly branched N-glycans at cell surface is correlated with the rapidness of tumor formation and altered adhesive properties of tumor cells in vivo.

3T3 Cells↗
PubMed1997

Control of Theileria sergenti infection by vaccination.

Bovine piroplasmosis caused by Theileria sergenti is a major cause of economic loss in grazing cattle in Japan. Infected calves show chronic anaemia with intraerythrocytic piroplasms and occasionally die in severe cases. We found that parasite stocks and isolates consist of genetically and antigenically mixed populations. To differentiate parasite populations bearing 3 allelic forms of p32/34, an immunodominant piroplasm surface protein, 3 sets of oligonucleotide primers were designed to amplify either of 3 alleles by polymerase chain reaction (PCR). By using this allele-specific PCR, we found that the majority of T. sergenti-infected calves in Japan harbored mixed parasite populations bearing C and I type parasites. To control Theileria infection, we produced 2 vaccine candidates: recombinant baculovirus p32 and synthetic peptide containing Lys-Glu-Lys (KEK) motif. Immunization with either recombinant p32 or synthetic peptide containing KEK sequences with Freund's complete adjuvant resulted in low parasitemia and reduced the clinical symptoms compared to control calves. Interestingly, the parasite with the p32 allelic form corresponding to the one used as the immunogen was suppressed.

Amino Acid Sequence↗
PubMed1997

The in vitro effects of all-trans-retinoic acid and hematopoietic growth factors on the clonal growth and self-renewal of blast stem cells in acute promyelocytic leukemia.

All-trans-retinoic acid (ATRA) has been used as a potent therapeutic agent to induce differentiation of acute promyelocytic leukemia (APL) cells, and granulocyte colony-stimulating factor (G-CSF) has been reported to enhance this effect of ATRA in vitro. We investigated the effects of ATRA and three myeloid growth factors, including G-CSF, on the growth of the leukemic stem cells of 10 APL patients. G-CSF was the most powerful stimulator of leukemic colony formation in five out of 10 patients, but was neither the major stimulant of self-renewal of the blast stem cells nor an inducer of maturation. In contrast, ATRA was highly effective in inducing morphological maturation of leukemic promyelocytes, but variable results were obtained in regard to its effects on the growth of blast stem cells: ATRA suppressed both clonal growth and self-renewal in some patients, but was inactive or even had stimulating effects in the other patients. Similar variable effects were observed with the combination of ATRA and G-CSF. These findings indicate that the differentiation-inducing effect of ATRA is not always associated with growth inhibition of leukemic stem cells in vitro and justify the use of chemotherapy in conjunction with ATRA in the treatment of APL.

Adolescent↗
PubMed1997

Quantitative assays for hepatitis C virus in serum as predictors of the long-term response to interferon.

BACKGROUND/AIMS: Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy. METHODS: HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype. RESULTS: From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicor-monitor and CRT-PCR, in contrast to 60% (187/312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r = 0.680 to 0.731). Serum HCV RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with < 1 x 10(4) copies/ml of HCV RNA by Amplicor-monitor assay, < 2 x 10(5) copies/ml by CRT-PCR, < 0.5 Meq/ml by bDNA assay, and < 20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (< 11%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype. CONCLUSIONS: Quantitation of HCV core protein and HCV RNA in useful for prediction of the interferon response.

Adolescent↗
PubMed1997

Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo-Chiba Hepatitis Research Group.

BACKGROUND & AIMS: The relative role of virus load and hepatitis C virus (HCV) subtype as predictor of the efficacy of interferon (IFN) therapy is still in dispute. To resolve this issue, a multicenter, randomized, prospective study of 272 patients with chronic hepatitis C but without cirrhosis was conducted. METHODS: The patients were randomly assigned to two different dose groups: 6 million units (MU) or 9 MU IFN three times a week for 6 months. Serum HCV RNA levels and HCV subtypes were determined. RESULTS: HCV RNA negativity rate at the completion of treatment with 9 MU IFN was higher than that with 6 MU (75% vs. 44%; P < 0.05). Virus eradication at 12 months after completion of treatment was higher in the 9 MU group than in the 6 MU group (36% vs. 25%; P < 0.05), especially in patients who had an intermediate virus load (10(4)-10(5) copies/mL by Amplicor monitor assay) (52% vs. 19%; P = 0.029). Virus eradication rate in patients with serotype 2 was higher than in those with serotype 1 for both regimens (6 MU, 53% vs. 15%; 9 MU, 76% vs. 29%; each P < 0.05). CONCLUSIONS: This prospective study showed that virus load, HCV serotype, and IFN dose are important predictors of the virological response to IFN therapy but virus load is the most important factor influencing the efficacy of IFN.

Adult↗