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Articles by Y Ando
Total Records ( 5 ) for Y Ando
  Y Ohya , H Jono , M Nakamura , S Hayashida , M Ueda , K Obayashi , S Misumi , K Asonuma , Y Ando and Y. Inomata
  Background

Some familial amyloidotic polyneuropathy (FAP) patients show the post-transplant progression of the clinical symptoms. Although the presence of recipient-derived cells in transplanted livers has been reported, no studies investigating the functional significance of this post-transplant chimerism in transplanted FAP patients were performed. The aims of this study were to evaluate amyloidogenic transthyretin (ATTR) production of recipient-derived cells and the relationship between the protein from recipient-derived cells and the progression of FAP symptoms after liver transplantation (LT).

Methods

Seven FAP ATTR Val30Met patients who underwent LT were included in this study. In one male patient with sex-mismatched donor, fluorescence in situ hybridization (FISH) method was performed on a liver biopsy sample using DNA probes for visualizing X and Y chromosomes to detect the recipient-derived cells. In three patients including the FISH-analysed patient, ATTR mRNA expression in transplanted livers was evaluated by the polymerase chain reaction (PCR)–restriction fragment length polymorphism method and realtime quantitative reverse transcription–PCR. In five of the seven patients, ATTR in serum protein expression was measured by mass spectrometry.

Results

One FAP patient has 3.1% recipient-derived cells in the transplanted liver. The ATTR mRNA was not expressed in any of the three transplanted livers. The ATTR was not detected in any sera of the sampled patients.

Conclusion

Although the FAP patient had recipient-derived cells in the transplanted liver, the recipient-derived cells did not contribute to the production of ATTR in our specific case. The effect of recipient-derived cells on the post-transplant progression of FAP symptoms may be negligible.

  R Hara , T Kawaji , E Ando , Y Ohya , Y Ando and H. Tanihara
 

Objective  To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients.

Methods  Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities—the most common ocular manifestation of FAP—in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis.

Results  Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not.

Conclusions  Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.

  K Fujita , H Nakayama , W Ichikawa , W Yamamoto , H Endo , F Nagashima , R Tanaka , T Miya , Y Sunakawa , K Yamashita , K Mizuno , H Ishida , K Araki , M Narabayashi , K Miwa , Y Ando , Y Akiyama , K Kawara , T Hirose and Y. Sasaki
 

S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase. We examined the effects of aging on the pharmacokinetics of the components of S-1. The median area under the concentration-time curve (AUC) of active 5-FU did not significantly differ between 10 patients 75 years or older and 53 patients younger than 75 years (P = 0.598, Mann-Whitney U test). It is interesting to note that the median oral clearance of tegafur in patients 75 years or older was significantly lower than that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC of CDHP was significantly higher in patients 75 years or older than in those younger than 75 years (P = 0.004). This effect was caused by reduced renal function in the elderly, because CDHP is excreted in the urine by glomerular filtration. The opposing effects of aging on the oral clearance of tegafur and the AUC of CDHP may offset each other, leading to unchanged systemic exposure of 5-FU.

  K Fujita , H Nakayama , W Ichikawa , W Yamamoto , H Endo , F Nagashima , R Tanaka , T Miya , Y Sunakawa , K Yamashita , K Mizuno , H Ishida , K Araki , M Narabayashi , K Miwa , Y Ando , Y Akiyama , K Kawara , T Hirose and Y. Sasaki
 

S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase. We examined the effects of aging on the pharmacokinetics of the components of S-1. The median area under the concentration-time curve (AUC) of active 5-FU did not significantly differ between 10 patients 75 years or older and 53 patients younger than 75 years (P = 0.598, Mann-Whitney U test). It is interesting to note that the median oral clearance of tegafur in patients 75 years or older was significantly lower than that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC of CDHP was significantly higher in patients 75 years or older than in those younger than 75 years (P = 0.004). This effect was caused by reduced renal function in the elderly, because CDHP is excreted in the urine by glomerular filtration. The opposing effects of aging on the oral clearance of tegafur and the AUC of CDHP may offset each other, leading to unchanged systemic exposure of 5-FU.

  A. M Burroughs , Y Ando , M. J. L de Hoon , Y Tomaru , T Nishibu , R Ukekawa , T Funakoshi , T Kurokawa , H Suzuki , Y Hayashizaki and C. O. Daub
 

Animal microRNA sequences are subject to 3' nucleotide addition. Through detailed analysis of deep-sequenced short RNA data sets, we show adenylation and uridylation of miRNA is globally present and conserved across Drosophila and vertebrates. To better understand 3' adenylation function, we deep-sequenced RNA after knockdown of nucleotidyltransferase enzymes. The PAPD4 nucleotidyltransferase adenylates a wide range of miRNA loci, but adenylation does not appear to affect miRNA stability on a genome-wide scale. Adenine addition appears to reduce effectiveness of miRNA targeting of mRNA transcripts while deep-sequencing of RNA bound to immunoprecipitated Argonaute (AGO) subfamily proteins EIF2C1–EIF2C3 revealed substantial reduction of adenine addition in miRNA associated with EIF2C2 and EIF2C3. Our findings show 3' addition events are widespread and conserved across animals, PAPD4 is a primary miRNA adenylating enzyme, and suggest a role for 3' adenine addition in modulating miRNA effectiveness, possibly through interfering with incorporation into the RNA-induced silencing complex (RISC), a regulatory role that would complement the role of miRNA uridylation in blocking DICER1 uptake.

 
 
 
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