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Biomedical subjects

A Takano

Publications and source records attributed to A Takano.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intrafamilial phenotypic variation in limb-girdle muscular dystrophy type 2C with compound heterozygous mutations.

Two Japanese-Brazilian siblings with type 2C limb girdle muscular dystrophy showed a maternal 521-T deletion in exon 6 and a larger paternal deletion of exon 6 in the gamma-sarcoglycan gene. One sib was ambulant at 29 years of age, whereas the other sib was confined to a wheelchair at the age of 12. Sarcoglycan staining of the muscle was reduced in both siblings but it did not correlate with the observed variability of the clinical severity.

Adult↗
PubMed2000

Tumor necrosis factor-alpha expression in muscles of polymyositis and dermatomyositis.

We evaluated the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in muscle biopsy specimens from patients with polymyositis (PM) and dermatomyositis (DM) to clarify its role in the pathogenesis of PM and DM. We performed non-radioactive in situ hybridization studies for TNF-alpha combined with immunohistochemistry for cell type-specific markers on muscles from ten PM and five DM patients. TNF-alpha-positive infiltrating cells present in the endomysium and perimysium were found in all PM and DM muscles. The frequency of TNF-alpha-positive cells against total infiltrating cells was similar among PM and DM (27.1 +/- 7.4% in PM and 28.5 +/- 13.6% in DM). However, TNF-alpha/CD8-positive lymphocytes and TNF-alpha-positive macrophages invading the non-necrotic muscle fiber were observed only in PM but not in DM. TNF-alpha was more highly expressed in PM and DM than was previously thought, and it was suggested that TNF-alpha plays a role in muscle fiber degeneration in PM.

Aged↗
PubMed2000

A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is a major substrate of the insulin receptor and acts as a docking protein for Src homology 2 domain containing signaling molecules that mediate many of the pleiotropic actions of insulin. Insulin stimulation elicits serine/threonine phosphorylation of IRS-1, which produces a mobility shift on SDS-PAGE, followed by degradation of IRS-1 after prolonged stimulation. We investigated the molecular mechanisms and the functional consequences of these phenomena in 3T3-L1 adipocytes. PI 3-kinase inhibitors or rapamycin, but not the MEK inhibitor, blocked both the insulin-induced electrophoretic mobility shift and degradation of IRS-1. Adenovirus-mediated expression of a membrane-targeted form of the p110 subunit of phosphatidylinositol (PI) 3-kinase (p110CAAX) induced a mobility shift and degradation of IRS-1, both of which were inhibited by rapamycin. Lactacystin, a specific proteasome inhibitor, inhibited insulin-induced degradation of IRS-1 without any effect on its electrophoretic mobility. Inhibition of the mobility shift did not significantly affect tyrosine phosphorylation of IRS-1 or downstream insulin signaling. In contrast, blockade of IRS-1 degradation resulted in sustained activation of Akt, p70 S6 kinase, and mitogen-activated protein (MAP) kinase during prolonged insulin treatment. These results indicate that insulin-induced serine/threonine phosphorylation and degradation of IRS-1 are mediated by a rapamycin-sensitive pathway, which is downstream of PI 3-kinase and independent of ras/MAP kinase. The pathway leads to degradation of IRS-1 by the proteasome, which plays a major role in down-regulation of certain insulin actions during prolonged stimulation.

3T3 Cells↗
PubMed2000

Alternate exon in the 5'-untranslated region of the human ACTH receptor gene.

The human ACTH receptor (ACTH-R) gene consists of two exons; the first encodes the 5'-untranslated region (UTR) and the second encodes part of the 5'-UTR, the entire coding region, and the whole of the 3'-UTR. While investigating the transcription initiation site of the human ACTH-R gene by 5'-rapid amplification of cDNA ends, we found a 157-bp alternate exon in the 5'-UTR. This newly identified exon was irrelevant to the alternate exon in the mouse ACTH-R gene which we reported previously.

5' Untranslated Regions↗
PubMed2000

[Qualitative study of municipalities' maternal and child health promotion planning].

From 1997, basic maternal and child health services have been provided through municipalities. The ministry of Health and Welfare has requested all municipalities to publish a MCH promotion plan. We conducted a qualitative analysis of important contents of the plans using an evaluation index of original dichotomous variables. Out of 3,256 municipalities, 2,873 developed the plans for MCH promotion. Most of the plans present descriptions of the significance of MCH promotion planning, goals of the plans, problems of current MCH statistics and services, and plans of providing services. The proportion was low for plans which have needs assessment of target population, indicators of evaluation of plans, description of the relationship between objectives and services, importance of objectives, action plans, specific chapter or evaluation of the plan, monitoring of the plan, and plans for informing public of the MCH plan. Therefore, the MCH promotion plans have weaknesses in evaluation and action. The MCH promotion plans of middle sized cities were more likely to have these important contents. We will continue to analyze the processes for producing of excellent MCH promotion plans to extract universal promoting factors for producing MCH promotion plans.

Child Health Services↗
PubMed1999

SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus.

To elucidate the mechanism of the circadian rhythm, genes differentially expressed during subjective day and night in the rat suprachiasmatic nucleus (SCN), a circadian oscillator in mammals, were surveyed by a differential display method. We isolated a novel gene, scop (SCN circadian oscillatory protein), that was expressed in a circadian manner in the SCN. SCOP protein is predominantly expressed in the brain and has domains including a pleckstrin homology domain, leucine-rich repeats, a protein phosphatase 2C-like domain and a glutamine-rich region. The structural feature of SCOP protein suggests its role in the intracellular signaling in the SCN.

Amino Acid Sequence↗
PubMed1999

Differential effects of palmitate on glucose uptake in rat-1 fibroblasts and 3T3-L1 adipocytes.

Non-esterified fatty acids are thought to be one of the causes for insulin resistance. However, the molecular mechanism of fatty acid-induced insulin resistance is not clearly known. In this study, we first examined the effect of palmitate on insulin signaling in 3T3-L1 adipocytes. We found that 1h treatment with 1 mmol/l palmitate had no effect on insulin binding, tyrosine phosphorylation of insulin receptors, 185 kDa proteins and Shc, and PI3 kinase activity in 3T3-L1 adipocytes. Then, the effects of palmitate on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocytes were compared with those in poorly differentiated 3T3-L1 cells and in HIRc-B cells. Palmitate treatment had no effect on MAP kinase activity in fully differentiated 3T3-L1 adipocytes, while it inhibited MAP kinase in poorly differentiated 3T3-L1 cells and HIRc-B cells. Glucose transport in 3T3-L1 adipocytes treated with palmitate for 1 h, 4 h and 16 h was higher than that in control cells, but palmitate treatment caused a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B cells. Palmitate treatment did not significantly affect basal and insulin-stimulated GLUT4 translocation. When the cells were treated with PD98059, a specific MEK inhibitor, insulin-stimulated glucose uptake was not affected in 3T3-L1 adipocytes, while it was almost completely inhibited in HIRc-B cells. These results suggest the primary effect of palmitate on adipocytes may not involve insulin resistance of adipocytes themselves.

3T3 Cells↗
PubMed1999

Risk of breast cancer in Japanese women with benign breast disease.

To investigate the risk of breast cancer development in women with benign breast disease (BBD), 387 screen-detected BBD women and 1,489 normal women, taken from participants in the breast cancer screening program during 1978-1986, were followed through 1991. While 2,811 person-years in the BBD group and 11,018 person-years in the normal group were accumulated, 5 women in the BBD group and 6 women in the normal group developed breast cancer. Using the Mantel-Haenszel method, relative risks (RR) were estimated for all women with BBD and women in some BBD types. Significantly elevated risk of breast cancer was observed in all women with BBD (RR = 3.26, 95% confidence interval (CI) 1.08-9.83). Women with proliferative BBD were at high risk of breast cancer (RR = 8.48, 95% CI 2.99-24.10), but no increased risk was observed for women with non-proliferative BBD (RR = 0.93, 95% CI 0.11-7.66). These results are consistent with those in high-risk countries for breast cancer. In the management of women with BBD, histopathological diagnosis of the breast lesion is essential and women with proliferative BBD should be followed up carefully.

Adult↗
PubMed1999

Proliferative fraction, bcl-1 gene translocation, and p53 mutation status as markers in mantle cell lymphoma.

The molecular genetic hallmark of mantle cell lymphomas (MCL) is the reciprocal translocation t(11;14)(q13;q32) which juxtaposes the bcl-1 proto-oncogene to one of the joining segments of the immunoglobulin heavy chain gene. This translocation is very common in MCL and occurs in up to 70% of these malignancies. Due to the aggressive nature of MCL, markers identifying tumor progression and clinical outcomes are necessary. In this study we examined whether a corroborative relation exists between p53 mutations, bcl-1 translocation, and the proliferative fraction in MCL. We evaluated the proliferative fraction, p53 gene status, and bcl-1 translocation in 21 patients with confirmed MCL. Controls consisted of normal DNA and 7 B-cell lymphomas. Immunohistochemical detection of Ki-67 was used to assess proliferative activity while molecular techniques were used to detect p53 mutations and the bcl-1 gene translocation. Reactivity to the monoclonal antibody Ki-67 on neoplastic cells ranged from 5% to 40% in typical MCL cases. The bcl-1 gene translocation was detected by PCR in 48% (10/21) of MCLs while no rearrangements were detected by PCR in case control DNA. Screening exons 5-8 of the p53 gene for mutations did not identify a single mutation in any of the MCL cases. No correlation was found between p53 mutations, the presence of a bcl-1 translocation, and the proliferative activity of neoplastic MCL cells. We conclude that these markers may demonstrate independent events which occur during the pathogenesis of MCL.

Aged↗
PubMed1999

[Experimental study on direct toxicity of combined cisplatin and methotrexate for normal and neoplastic cell lines].

The combination effect of cisplatin (CDDP) and methotrexate (MTX) on the cytotoxicity against normal fibroblast and malignant cell line were investigated utilizing MTT assay. In case of normal fibroblast, the optical density (OD) value in CDDP + MTX was significantly higher and remained at a consistently higher value in various mixture rates than that in CDDP alone. Such low cytotoxicity may be due to MTX because the addition of Leucovorin resulted in an apparent decrease in the OD value. The combination of the two drugs was thought to alleviate the toxicity of CDDP on fibroblast, in contrast to its increase on cancer cells.

Animals↗
PubMed1999

[Visualization of normal organs in whole-body FDG-PET imaging].

It is important to know FDG accumulation in the normal distributions for interpreting whole-body PET imaging for tumor detection. Twenty-eight normal subjects were studied with whole-body PET imaging and were examined the intensity of FDG uptake in major organs and the factors which caused it's variety. Emission images were acquired and images were reconstructed without attenuation correction. The intensity of FDG uptake was classified into 4 grades visually. No accumulation was found in the thyroid, the esophagus and the spleen. The oral cavity, the liver, the stomach, and the colon were visualized in all subjects. The laryngeal muscle, the cervical muscle, and the heart accumulated FDG with various grade from 1 to 4 grades. No association was found between the intensity of uptake in the organs and volunteer's age. The fasting time was shorter in volunteers whose heart showed "high" grade than those showed less accumulation (p < 0.05). Serum concentration of free fatty acid was significantly lower in them, too (p < 0.05). Various FDG uptake was observed in many organs, especially the laryngeal muscle, the cervical muscle, and the heart. In our study, there was no facter which caused FDG uptake in organs except for the fasting time and the value of free fatty acid in the heart. Such analysis of whole-body FDG distributions in the normal subjects is valuable for tumor detection with FDG-PET.

Adult↗
PubMed1999

[Direct Gram staining of blood culture sample enabled the early diagnosis of brain abscess due to Listeria monocytogenes].

A 58 year old woman had a long history of immunocompromised state. Since age 28 she had multiple endocrine neoplasm type 2A: her thyroid gland and bilateral adrenal glands were removed because of pheochromocytoma and thyroid medullary carcinoma. Corticosteroid and levothyroxine were supplemented. At age 57 she was afflicted with systemic lupus erythematodes and nephrotic syndrome. Prednisolone therapy was started. Two months later she developed fever, lethergy, headache and left hemiparesis. MRI revealed multiple ring-enhancing lesions in the right cerebrum. CSF was negative for microorganisms. Blood culture hemolysed after 24 hours. Direct gram staining of the blood culture sample revealed gram-positive short rods without spore, suggested listeria. This enabled prompt initiation of high dose penicillin therapy before the official report of listseria infection. Neurological abnormality including left hemiparesis disappeared completely within one month. Enhancement of abscess wall decreased every month, but it persisted for five months despite continuous intravenous penicillin therapy. Listeria monocytogenes is well-recognized as an opportunistic pathogen. It requires prolonged therapy with antibiotics, since it is the intracellular organism. Monitoring of the brain abscess wall by the enhanced MRI is useful to determine the completion of therapy. Since listerial contamination is common among raw meat and unpasteurized milk, immunocompromised patients should be alarmed not to eat uncooked food products.

Bacteriological Techniques↗
PubMed1998

Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat1 fibroblasts expressing insulin receptors.

Shc is phosphorylated on Tyr-239/240 and/or Tyr-317, which serves as a docking site for Grb2. To clarify the relative involvement of Shc Tyr-239/240 and Tyr-317 in insulin-induced mitogenesis, we generated expression vectors for Y317F (1F)-Shc, Y239/240F (2F)-Shc, and Y239/240/317F (3F)-Shc, and stably transfected them into Rat1 fibroblasts expressing insulin receptors (HIRc). Insulin-induced Shc phosphorylation and subsequent association with Grb2 was enhanced in wild-type (WT)-Shc cell. In contrast, insulin-stimulated Shc phosphorylation and Shc.Grb2 association were significantly decreased in 1F-Shc and 3F-Shc cells, while these were only slightly affected and almost comparable in 2F cells compared with those in parental HIRc cells. The kinetics of MAP kinase activation closely paralleled the kinetics of Shc phosphorylation and Shc.Grb2 association. Thus, insulin stimulation of MAP kinase activation occurred more rapidly in WT-Shc cells, and the activation was delayed in 1F-Shc and 3F-Shc cells, while it was comparable in 2F-Shc cells compared with that in HIRc cells. Furthermore, WT-Shc cells displayed enhanced sensitivity to insulin stimulation of thymidine incorporation. Importantly, the sensitivity was significantly decreased in 1F-Shc and 3F-Shc cells, while it was almost comparable in 2F-Shc cells compared with that in HIRc cells. These results indicate that Shc Tyr-317 is more predominant insulin-induced phosphorylation site than Tyr-239/240 for coupling with Grb2 leading to MAP kinase activation and mitogenesis in Rat1 fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1998

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗
PubMed1998

Cloning and characterization of a cDNA encoding a novel heterogeneous nuclear ribonucleoprotein-like protein and its expression in myeloid leukemia cells.

We isolated a cDNA encoding a novel heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein on DNA affinity screening of a K562 cDNA expression library with an oligodeoxynucleotide (JKT41) derived from intron 9 of the human myeloperoxidase gene. The cDNA has a 1,305 bp sequence that encodes a polypeptide of 301 amino acid residues. The protein, named JKTBP, contains two repeats of a putative RNA binding domain (RBD), each composed of canonical RNP-2 and RNP-1 motifs, and a glycine- and tyrosine-rich carboxyl terminus. The sequences of these two repeats are highly homologous with those of the 2 x RBD-Gly rich group of hnRNPs. Northern blotting showed that two mRNAs of approximately 1.4 and 2.8 kb were present in most cultured cells examined. The recombinant protein expressed in Escherichia coli interacted with the double-stranded form of JKT41 as well as with its single-stranded form. This interaction was competitively inhibited by the same unlabeled JKT41 and to nearly the same extent by unrelated oligonucleotides. Moreover, the recombinant protein interacted with poly(G) and poly(A), but not with poly(U) or poly(C). Transient expression of the protein in SKM-1 cells repressed the expression of chloramphenicol acetyltransferase reporter genes located downstream of the intron 9 element of JKT41 or intron 7 element of FERE27. The implications of the protein in the biogenesis of mRNA are discussed.

Amino Acid Sequence↗
PubMed1998

Development of melanocyte progenitors in murine Steel mutant neural crest explants cultured with stem cell factor, endothelin-3, or TPA.

Stem cell factor (SCF) has been suggested to be indispensable for the development of neural crest cells into melanocytes because Steel mutant mice (i.e., Sl/Sl(d)) have no pigmented hairs. On the other hand, it has been demonstrated that the addition of endothelin 3 (ET-3) or TPA to neural crest cell cultures can induce melanocyte differentiation without addition of extrinsic SCF. In this study, we excluded the influence of intrinsic SCF by using Sl/Sl mouse embryos to study more precisely the effects of natural cytokines, such as extrinsic soluble SCF or ET-3, or chemical reagents, such as TPA or cholera toxin. We found that SCF is supplied within the wild-type neural crest explants and that ET-3 cannot induce melanocyte differentiation or proliferation without SCF. These results indicate that SCF plays a critical role in survival or G1/S entry of melanocyte progenitors and that SCF initially stimulates their proliferation and then ET-3 accelerates their proliferation and differentiation. TPA has the ability to elicit neural crest cell differentiation into melanocytes without exogenously added SCF but it is not as effective as SCF because many more melanocytes developed in the wild-type neural crest explants cultured with TPA.

Animals↗