Biomedical subjects

Naoyuki Shimada

Publications and source records attributed to Naoyuki Shimada.

4 recordsLinked to original sources

PubMed2005

Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis.

We developed a thyroid hormone (TH) inducible primary screening assay for the identification and assessment of man-made chemicals that interfere with the TH-signalling pathway within target cells. The assay was developed in a Xenopus laevis cell line that was transduced with a self-inactivating (SIN) lentivirus vector (LV) containing a luciferase gene. The luciferase activation in this cell line was TH-specific: 3,3',5-L-triiodothyronine (T(3)) > 3,3'5-L-triiodothyroacetic acid (Triac) > 3,3',5-D-triiodothyronine (D-T(3)), > L-thyroxine (T(4)) > 3,3',5'-L-triiodothyronine (rT(3)). The application of the ligand-dependent luciferase assay for screening for thyroid system-disrupting chemicals revealed that three phthalates (dicyclohexyl phthalate, n-butylbenzyl phthalate, and di-n-butyl phthalate), two herbicides (ioxynil and pentachlorophenol) and a miticide (dicofol) had 3,3',5-L-triiodothyronine- T(3)- antagonist activity at concentrations ranging from 10(-6) to 10(-5) M. These chemicals also inhibited the expression of the endogenous primary T(3)-response TH nuclear receptor beta (TRbeta) gene. The inhibitory characteristics of these chemicals were similar for both assays performed, although the assay for T(3)-dependent activation of TRbeta gene was more sensitive than the luciferase assay. These results indicate that the luciferase assay was a rapid method with a small intra-assay variation for the primary screening of thyroid system-disrupting chemicals. Of the six chemicals, only n-butylbenzyl phthalate and pentachlorophenol exhibited T(3)-antagonist activity in an in vivo metamorphosis-based assay. It should be noted that chemicals elicited thyroid system-disrupting activity in the luciferase assay did not always interfere with the thyroid system in vivo.

Animals↗

PubMed2005

Identification of thyroid hormone-responsive genes in a chicken hepatoma cell line, LMH.

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate the transcription of multiple thyroid hormone (TH)-responsive genes. Our study aimed to identify TH-responsive genes in an estrogen-responsive chicken hepatoma cell line, LMH. RNA was prepared from cells treated with or without 10(-8) M 3,3',5-triiodothyronine (T3) for 24 h and was analyzed by differential display. At least six cDNAs were detected whose transcript increased in the presence of T3, and four of them were cloned. The four candidate TH-responsive genes that were identified had high similarity (>83%) to known chicken or mammalian genes, which included the ribosomal protein L7 gene; the cytoplasmic dynein heavy chain gene; the scaffold attachment factor A (SAF-A) gene, also known as heterogeneous nuclear ribonucleoprotein U (hnRNP U); and a gene for an unknown protein. Real-time PCR confirmed that the transcription of the four genes was responsive to T3; their transcript levels increased from four to eleven times with the administration of T3. The amount of TRbeta transcript did not change with the administration of T3. The physiological reasons for the activation of these genes and the utility of this cell line are discussed.

Animals↗

PubMed2003

Multifunctional gratings for surface-emitting lasers: design and implementation.

We experimentally demonstrate the use of two different multifunctional grating couplers in surface-emitting lasers for improved beam quality and advanced beam profiles. The lasers used for the demonstration are grating-based unstable resonator lasers, each with a grating coupler for surface emission and beam shaping. The new design method, described in detail, allows for simultaneous optimization of arbitrary feedback and outcoupling characteristics of the grating coupler. The first coupler is designed to reduce feedback to the resonator that would otherwise disturb the operation of the laser and lower the beam quality and to produce an output beam focused to four spots. The second coupler is designed to provide the feedback needed to support the unstable resonator, eliminating one feedback grating, and simultaneously focus the output beam to a single spot. As far as we know, this is the first time such multifunctional couplers are used in grating-coupled surface-emitting lasers. The couplers provide near-diffraction-limited spots that are a considerable improvement compared with previous lasers with no feedback control in the couplers.

Journal Article↗

PubMed2002

The effects of endocrine-disrupting chemicals on thyroid hormone binding to Xenopus laevis transthyretin and thyroid hormone receptor.

We investigated the effects of medical, industrial and agricultural chemicals on 3,3',5-L-[125I]triiodothyronine ([125I]T3) binding to purified recombinant Xenopus laevis (X. laevis) transthyretin (xTTR), a plasma thyroid hormone-binding protein, and to the ligand-binding domain of thyroid hormone receptor-beta (xTR LBD). xTTR derived from X. laevis serum had about 80 times higher affinity for T3 than for L-thyroxine. The xTTR's relative affinities for diethylstilbestrol, pentachlorophenol and ioxynil were 10(-1)- to 10(-2)-fold less than that for T3. However, all chemicals investigated had either a weak or no influence on [125I]T3 binding to xTR LBD. The concentration of diethylstilbestrol, the most potent chemical, required for 50% inhibition of [125I]T3 binding to xTR LBD was 10(4) times greater than that of unlabeled T3. These results indicate the existence of several chemicals that interact with xTTR but not with xTR LBD.

Animals↗