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Hirokazu Takahashi

Publications and source records attributed to Hirokazu Takahashi.

At least 19 recordsLinked to original sources
PubMed2025

Long-Term Effectiveness of Tenofovir Alafenamide Versus Entecavir in Treatment-Naive Chronic Hepatitis B: A Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus.

INTRODUCTION: Although both tenofovir alafenamide (TAF) and entecavir (ETV) are recommended first-line treatments for chronic hepatitis B, comparative data on their effectiveness remain limited. We aim to compare their virologic (VR), biochemical (BR), and complete (CR) response rates. METHODS: This retrospective study enrolled treatment-naive chronic hepatitis B patients who initiated either TAF or ETV in 2016 or after across 22 international centers and evaluated their treatment response after balancing their characteristics using inverse probability treatment weighting and through Fine-Gray competing-risks analysis of the balanced cohort. RESULTS: The study included 1,605 patients (784 TAF and 821 ETV patients with significant background differences) of whom 1,553 (96.8%) were from Asia. Inverse probability treatment-weighting analysis yielded a total weighted cohort of 1,660 (822 TAF and 838 ETV patients with balanced characteristics). The 5-year cumulative VRs were high in both groups with a slightly higher rate in TAF patients (98.0% vs 93.9%, P < 0.001), and similar findings were found in a subgroup analysis by median hepatitis B virus (HBV) DNA (5.5 log IU/mL). However, there was no significant difference in the 5-year BR rates overall (93.7 vs 92.8%, P = 0.484) or by alanine aminotransferase (ALT) cutoff of 2&#xd7; upper limit of normal. TAF patients had a slightly higher 5-year cumulative CR overall (94.9% vs 89.4%, P = 0.001) and in high HBV DNA (96.9% vs 87.9%, P < 0.001) or ALT &#x2265;2&#xd7; upper limit of normal patients (97.3% vs 90.6%, P < 0.001), but not in those with lower HBV DNA or ALT. DISCUSSION: BR rates were similar with ETV and TAF, while VR and CR were higher with TAF, although the difference was modest (<5% overall, 7%-9% in high HBV DNA or ALT groups). Antiviral selection between TAF vs ETV should be based mainly on cost, side effect profile, and patient preference.

Adult↗
PubMed2007

PPARgamma inhibitors reduce tubulin protein levels by a PPARgamma, PPARdelta and proteasome-independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells.

The nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been identified as an important therapeutic target in murine models of colorectal cancer (CRC). To examine whether PPARgamma inhibition has therapeutic effects in late-stage CRC, the effects of PPARgamma inhibitors on CRC cell survival were examined in CRC cell lines and a murine CRC model. Low doses (0.1-1 microM) of PPARgamma inhibitors (T0070907, GW9662 and BADGE) did not affect cell survival, while higher doses (10-100 microM) of all 3 PPARgamma inhibitors caused caspase-dependent apoptosis in HT-29, Caco-2 and LoVo CRC cell lines. Apoptosis was preceded by altered cell morphology, and this alteration was not prevented by caspase inhibition. PPARgamma inhibitors also caused dual G and M cell cycle arrest, which was not required for apoptosis or for morphologic alterations. Furthermore, PPARgamma inhibitors triggered loss of the microtubule network. Notably, unlike other standard antimicrotubule agents, PPARgamma inhibitors caused microtubule loss by regulating tubulin post-transcriptionally rather than by altering microtubule polymerization or dynamics. Proteasome inhibition by epoxomicin was unable to prevent tubulin loss. siRNA-mediated reduction of PPARgamma and PPARdelta proteins did not replicate the effects of PPARgamma inhibitors or interfere with the inhibitors' effects on apoptosis, cell cycle or tubulin. PPARgamma inhibitors also reduced CRC cell migration and invasion in assays in vitro and reduced both the number and size of metastases in a HT-29/SCID xenograft metastatic model of CRC. These results suggest that PPARgamma inhibitors are a novel potential antimicrotubule therapy for CRC that acts by directly reducing microtubule precursors.

Amino Acid Chloromethyl Ketones↗
PubMed2007

Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer.

We investigated whether leukotriene B(4) (LTB(4)) and its signaling pathway play an important role in the progression of human colon cancer via a direct stimulation of cancer cell proliferation. Remarkable expression of LTB(4) receptor 1 (BLT1) in human colon cancer tissues was detected by immunohistochemistry, and Western blot analysis revealed the BLT1 expression in cultured human colon cancer cell lines, Caco2 and HT29. The 5-lipoxygenase inhibitor AA-861 and LTB(4)-receptor antagonist U75302 showed negative effects on survival and proliferation of both Caco2 and HT-29 cells. The inhibition of cell proliferation is due to the apoptosis because nuclear condensation and increased annexin V expression were observed in the cells treated with AA-861 and U75302. Knockdown of BLT1 by small interfering RNA caused the suppression of BLT1 protein, resulting in the inhibition of cancer cell proliferation. Blockade of BLT1 by the receptor antagonist significantly suppresses the LTB(4)-stimulated extracellular signal-regulated kinase (ERK) activation in colon cancer cells. These results indicate that the blockade of the LTB(4)-signaling pathway induces apoptosis via the inhibition of ERK activation in colon cancer cells. The LTB(4)-signaling pathway might be a new therapeutic target for colon cancer.

Apoptosis↗
PubMed2007

Ethylene promotes submergence-induced expression of OsABA8ox1, a gene that encodes ABA 8'-hydroxylase in rice.

A rapid decrease of the plant hormone ABA under submergence is thought to be a prerequisite for the enhanced elongation of submerged shoots of rice (Oryza sativa L.). Here, we report that the level of phaseic acid (PA), an oxidized form of ABA, increased with decreasing ABA level during submergence. The oxidation of ABA to PA is catalyzed by ABA 8'-hydroxylase, which is possibly encoded by three genes (OsABA8ox1, -2 and -3) in rice. The ABA 8'-hydroxylase activity was confirmed in microsomes from yeast expressing OsABA8ox1. OsABA8ox1-green fluorescent protein (GFP) fusion protein in onion cells was localized to the endoplasmic reticulum. The mRNA level of OsABA8ox1, but not the mRNA levels of other OsABA8ox genes, increased dramatically within 1 h after submergence. On the other hand, the mRNA levels of genes involved in ABA biosynthesis (OsZEP and OsNCEDs) decreased after 1-2 h of submergence. Treatment of aerobic seedlings with ethylene and its precursor, 1-aminocyclopropane-1-carboxylate (ACC), rapidly induced the expression of OsABA8ox1, but the ethylene treatment did not strongly affect the expression of ABA biosynthetic genes. Moreover, pre-treatment with 1-methylcyclopropene (1-MCP), a potent inhibitor of ethylene action, partially suppressed induction of OsABA8ox1 expression under submergence. The ABA level was found to be negatively correlated with OsABA8ox1 expression under ACC or 1-MCP treatment. Together, these results indicate that the rapid decrease in ABA levels in submerged rice shoots is controlled partly by ethylene-induced expression of OsABA8ox1 and partly by ethylene-independent suppression of genes involved in the biosynthesis of ABA.

Base Sequence↗
PubMed2007

Prospective evaluation of factors associated with post-LASIK corneal birefringence with scanning laser polarimetry.

PURPOSE: To identify factors that affect corneal birefringence, such as the corneal polarization axis (CPA) and corneal polarization magnitude (CPM), after laser in situ keratomileusis (LASIK) using scanning laser polarimetry with a variable corneal polarization compensator. METHODS: The CPA and CPM from 42 patients (42 eyes) who underwent LASIK and 24 normal untreated subjects (24 eyes) were measured 1 week before and 1 week after LASIK. Changes in the CPA and CPM after LASIK were studied using Student t test and Pearson correlation coefficient. RESULTS: In the LASIK group, the post-LASIK CPA and CPM significantly changed, whereas both values did not change in normal subjects. Among 5 candidate factors [preoperative CPA (pre-CPA), preoperative CPM (pre-CPM), age, change in corneal curvature, and ablation depth], the change in CPA was significantly correlated with the pre-CPA (r=-0.793) and pre-CPM (r=0.339). The change in CPM was correlated with the pre-CPA (r=-0.455) and pre-CPM (r=-0.411). Over 83% case of postoperative corneal birefringence can be explained by only 2 parameters with regression analysis. CONCLUSIONS: The pre-CPA and pre-CPM are strongly associated with LASIK-induced changes in CPA and CPM. Variations in age, changes in corneal curvature, and ablation depth do not contribute to changes in either parameter.

Adolescent↗
PubMed2006

Cell type-specific gene expression profiling in plants by using a combination of laser microdissection and high-throughput technologies.

Laser microdissection (LM) allows for the isolation of specific cells of interest from heterogeneous tissues under direct microscopic visualization with the assistance of a laser beam. By permitting global analyses of gene expression and metabolites in the selected cells, it is a powerful tool for understanding the biological processes in individual cell types during development or in response to various stimuli. Recently, LM technology has been successfully applied to the separation of individual plant cell types. Here, we provide an overview of applications of LM combined with high-throughput technologies including transcript analyses [microarrays, serial analysis of gene expression (SAGE) and 454-sequencing], proteomic analyses and metabolomic profiling, for cell type-specific gene expression analyses in plants.

Gene Expression Profiling↗
PubMed2006

More than 40,000 transcripts, including novel and noncoding transcripts, in mouse embryonic stem cells.

To study the transcriptome of embryonic stem cells, we used a new gene expression profiling method that can measure the expression levels of unknown and rarely expressed transcripts precisely. We detected a total of 33,136 signal peaks representing transcripts in mouse embryonic stem cells, E14. Subsequent random cloning of the peaks suggests that mouse embryonic stem cells express at least 40,000 transcripts, of which about 2,000 are still unknown. In addition, we identified 1,022 noncoding transcripts, several of which change depending on differentiation in gene expression. Our database provides a high-resolution expression profile of E14 cells and is applicable to other mouse embryonic stem cell analyses. It includes most transcription regulation factor-encoding genes and a significant number of unknown and noncoding transcripts.

Animals↗
PubMed2006

Inhibition of peroxisome proliferator-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties.

Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.

Actins↗
PubMed2006

Selection between pinching-type and supramolecular polymer-type complexes by alpha-cyclodextrin-beta-cyclodextrin hetero-dimer and hetero-cinnamamide guest dimers.

Novel supramolecular complexes have been prepared from an alpha-cyclodextrin-beta-cyclodextrin hetero-dimer (alpha-CD-beta-CD hetero-dimer) and hetero-cinnamamide guest dimers, G-t-Boc and G-NH2, having adamantyl groups in aqueous solutions. On addition of the competitive guest, the supramolecular structure formed by a mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc was found to be different from that of a mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 by the 1H NMR spectroscopy, the ROESY NMR spectroscopy, and the circular dichroism spectroscopy. The size of the supramolecular complex from the mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 is larger than that from the mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc, which was proved by the pulse field gradient spin-echo NMR and the atomic force microscopy. These results suggest that the mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc formed a pinching-type complex, and the mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 formed a supramolecular polymer-type complex.

Cinnamates↗
PubMed2006

Identification of genes that express in response to light exposure and express rhythmically in a circadian manner in the mouse suprachiasmatic nucleus.

Most biological phenomena, including behavior and metabolic pathways, are governed by an internal clock system that is circadian (i.e., with a period of approximately 24 h) and is reset by light exposure from outside. In order to understand the molecular basis of the resetting mechanism of the clock, we attempted to isolate light-inducible transcripts in the suprachiasmatic nucleus, where the master clock resides, using a new gene expression profiling procedure. We identified 87 such transcripts, successfully cloned 60 of them and confirmed their light inducibility. Six of the 60 were already known to be light inducible and 17 are protein-coding transcripts registered in the public database that were not known to be light inducible. Induction is subjective night specific in most of the transcripts. Interestingly, 6 of the transcripts exhibit rhythmic expression in a circadian manner in the suprachiasmatic nucleus.

Animals↗
PubMed2006

Intracerebroventricular injection of neuropeptide Y modifies carbohydrate and lipid metabolism in chicks.

The purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of neuropeptide Y (NPY) affects heat production (HP), body temperature, and plasma concentrations of metabolic fuels in chicks. ICV injection of NPY (0, 188 or 375 pmol) did not affect HP, but significantly lowered respiratory quotient as well as the rectal temperature. These data suggest that the energy sources for HP were modified by NPY in the body. This idea was confirmed by subsequent experiments in which ICV injection of NPY significantly reduced plasma glucose and triacylglycerol concentrations but increased non-esterified fatty acid concentrations. The effect of NPY on the utilization of metabolic fuels was not associated changes in plasma catecholamine and corticosterone concentrations. In summary, the present study demonstrated that central NPY modifies peripheral carbohydrate and lipid metabolism in chicks.

Animals↗
PubMed2006

Thyrotropin-releasing hormone increased heat production without the involvement of corticotropin-releasing factor in neonatal chicks.

Thyrotropin-releasing hormone (TRH) is a hypothalamic signal in the hypothalamic-pituitary-thyroid (HPT) axis, and is well known as a hyperthermic hormone in the brain of chicks. The thermogenetic effect leads to the hypothesis that central TRH increases heat production (HP) in chicks. The purpose of the present study was to clarify whether central TRH affects HP of neonatal chicks, and if such an effect is mediated by corticotropin-releasing factor (CRF) since the thermogenetic effect of TRH is mediated by CRF. Intracerebroventricular (ICV) injection of TRH (14 and 55 nmol) dose-dependently increased oxygen consumption, carbon dioxide production and HP, and a similar effect was also observed with CRF (2.1 and 21 pmol). The TRH-induced increase in HP could not be attenuated by astressin, a CRF receptor antagonist, while the effect of CRF was completely diminished by astressin. The present study demonstrates that central TRH increases HP in chicks but the effect was not related to CRF.

Animals↗
PubMed2006

A wide-range phylogenetic analysis of Zic proteins: implications for correlations between protein structure conservation and body plan complexity.

We compared Zic homologues from a wide range of animals. Striking conservation was found in the zinc finger domains, in which an exon-intron boundary has been kept in all bilateralians but not cnidarians, suggesting that all of the bilateralian Zic genes are derived from a single gene in a bilateralian ancestor. There were additional conserved amino acid sequences, ZOC and ZF-NC. Combined analysis of the zinc finger, ZOC, and ZF-NC revealed the presence of two classes of Zic, based on the degree of protein structure conservation. The "conserved" class includes Zic proteins from the Arthropoda, Mollusca, Annelida, Echinodermata, and Chordata (vertebrates and cephalochordates), whereas the "diverged" class contains those from the Platyhelminthes, Cnidaria, Nematoda, and Chordata (urochordates). The result indicates that the ancestral bilateralian Zic protein had already acquired an entire set of conserved domains, but that this was lost and diverged in the platyhelminthes, nematodes, and urochordates.

Amino Acid Sequence↗
PubMed2006

Diabetes-associated retinal nerve fiber damage evaluated with scanning laser polarimetry.

PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus compared with age-matched normal control subjects, to assess the correlation between the RNFL thickness and the severity of retinopathy, and to investigate whether diabetes mellitus is a potential source of abnormal results in glaucoma screening or evaluation with scanning laser polarimetry (SLP). DESIGN: Cross-sectional analysis of normal and diabetic eyes. METHODS: setting: Institutional clinical study. patients: One hundred twenty-eight subjects with type 2 diabetes mellitus and 50 age-matched normal control subjects without glaucoma or glaucoma-suspect. All patients underwent imaging with SLP and repeatable automated perimetry. Subjects with diabetes mellitus were classified into four stages on the basis of the severity of retinopathy that was assessed by dilated funduscopic examination, high-quality fundus color photography, and fluorescein angiography. MAIN OUTCOME MEASURES: The SLP (GDx VCC software, version 5.5.0) parameters. RESULTS: The RNFL thickness in patients with diabetes mellitus was reduced significantly compared with age-matched normal control eyes (P < .01). Moreover, all RNFL thickness parameters of the GDx VCC software decreased significantly as an exacerbation of diabetic retinopathy (P = .0019, P = .0045, P = .0010 for temporal-superior-nasal-inferior-temporal (TSNIT) average, superior average, inferior average, respectively). The nerve fiber indicator also increased significantly (P < .0001), despite an absence of glaucomatous optic nerve damages. CONCLUSION: The RNFL thickness in type 2 diabetes mellitus, which was measured by GDx VCC software, significantly decreased with the severity of diabetic retinopathy. The presence of diabetes mellitus can be a source of false-positive results and overestimation of glaucomatous optic neuropathy when eyes are screened with GDx VCC software.

Aged↗
PubMed2006

Phaco-viscocanalostomy versus phaco-trabeculotomy: a middle-term study.

PURPOSE: To compare the surgical outcomes between phaco-viscocanalostomy and phaco-trabeculotomy in open-angle glaucoma. PATIENTS AND METHODS: In a nonrandomized, retrospective clinical study, 110 eyes underwent phaco-viscocanalostomy (VCS group), and 110 eyes underwent phaco-trabeculotomy (LOT group). The mean follow-up was 857+/-409 (+/-SD) days (P=0.4777). RESULTS: The mean preoperative treated intraocular pressure (IOP) values were 20.2+/-3.5 mm Hg in the VCS group and 20.9+/-3.5 mm Hg in the LOT group (P=0.3377). The postoperative IOPs in the VCS group were 15.0+/-3.0 and 16.1+/-3.0 mm Hg at 1 and 3 years, and in the LOT group 16.3+/-2.9 mm Hg (P=0.0088) and 16.5+/-3.3 mm Hg (P=0.4993), respectively. The number of medications used in the VCS group was significantly lower than in the LOT group during the observation periods (P< or =0.0130). The probabilities of achieving IOPs< or =21 mm Hg at 3 years in the VCS group were 92.0% with or without mediations and 58.2% without medications, and were significantly better than those of the LOT group (84.7% and 36.0%, P=0.0334 and P<0.0001 by log-rank test, respectively). The probabilities of achieving IOPs< or =16 mm Hg at 3 years in the VCS group were 30.5% with or without mediations and 30.3% without medications, whereas those in the LOT group were 27.5% (P=0.1799) and 19.4% (P=0.0010), respectively. The visual outcome was similar between the groups. Postoperative hyphema (> or =2 mm) and IOP spikes (> or =30 mm Hg) occurred significantly less in the VCS group (2.7 and 3.6%, respectively) than in the LOT group (26.4 and 28.2%, respectively; P<0.0001). In 13 eyes (11.8%) of the LOT group, the highest IOP level was recorded 40 mm Hg or higher. Vitreous hemorrhage and central visual loss occurred in 1 case each in the LOT group. CONCLUSIONS: After a middle-term observation, phaco-viscocanalostomy provides better IOP control and a lower incidence of vision-threatening complications than phaco-trabeculotomy.

Aged↗
PubMed2006

Effects of poly-L-arginine on the permeation of hydrophilic compounds through surface ocular tissues.

We investigated whether poly-L-arginine (PLA) could improve permeation of the hydrophilic compounds, FITC-labeled dextran (MW 3800, FD-4) and pyridoxamine, through ocular surface tissues. Samples of cornea, conjunctiva, or conjunctiva/sclera composite from Japanese white rabbits were mounted in Ussing chambers to measure FD-4 and pyridoxamine permeation and transepithelial electric resistance (TEER). The integrity and viability of the conjunctiva were assessed by chronological TEER monitoring and MTT assay, respectively. The permeability coefficient (Papp) of FD-4 in the cornea, conjunctiva, and conjunctiva/sclera composite was increased by the addition of PLA (MW 38 kDa, PLA (50) at 0.1 mg/ml by 6.81-, 9.78-, and 7.91-fold, respectively. The Papp of pyridoxamine was also increased in the presence of PLA (50) by 7.98-, 4.67-, 8.31-fold, respectively. A corresponding reduction in TEER was observed in all tissues. However, the reduced TEER in the case of the conjunctiva had recovered to ca. 70% 120 min after replacing the mucosal fluid with fresh bicarbonated Ringer's solution. MTT assay results indicated that treatment of the conjunctiva with 0.1 mg/ml PLA (50) did not change the production of formazan compared to that without PLA (50), indicating that the conjunctival viability is not significantly affected by PLA (50). Our findings suggest that PLA may be useful in promoting the ocular delivery of hydrophilic drugs without producing significant epithelial damage.

Animals↗