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Biomedical subjects

Kuniaki Arai

Publications and source records attributed to Kuniaki Arai.

7 recordsLinked to original sources
PubMed2006

Virological effects and safety of combined double filtration plasmapheresis (DFPP) and interferon therapy in patients with chronic hepatitis C: A preliminary study.

PURPOSE: In patients with chronic genotype 1b hepatitis C and a high viral load, the viral load was reduced by double filtration plasmapheresis (DFPP), followed by combined interferon and ribavirin therapy. The safety and virological effects of this treatment method were preliminarily investigated. METHODS: In nine patients with chronic hepatitis C, DFPP was performed three times on days 1, 2, and 4, and the administration of interferon and ribavirin was initiated immediately after DFPP on day 1. RESULT: The HCV RNA was undetectable in all patients after the plasma was passed through a plasma fractionator (second filter) in the DFPP circuit. After 2 weeks, the HCV RNA tended to decrease in the DFPP group more than in the control group (-2.45+/-1.12 versus -1.57+/-0.95, P=0.073). However, this decrease was not attributable to a sustained virological response (SVR) (22.2% versus 18.2%, P=0.822). Most of the adverse events were caused by the interferon and ribavirin combination therapy. CONCLUSION: DFPP can be safely performed concomitantly with interferon and ribavirin combination therapy in chronic hepatitis C patients. The combination may contribute to an early virological response. The effect of DFPP on the SVR and its significance remain to be clarified.

Journal Article↗
PubMed2006

Cytotoxic T cell responses to human telomerase reverse transcriptase in patients with hepatocellular carcinoma.

Human telomerase reverse transcriptase, hTERT, has been identified as the catalytic enzyme required for telomere elongation. hTERT is expressed in most tumor cells but seldom expressed in most human adult cells. It has been reported that 80% to 90% of hepatocellular carcinomas (HCCs) express hTERT, making the enzyme a potential target in immunotherapy for HCC. In the current study, we identified hTERT-derived, HLA-A*2402-restricted cytotoxic T cell (CTL) epitopes and analyzed hTERT-specific CTL responses in patients with HCC. Peptides containing the epitopes showed high affinity to bind HLA-A*2402 in a major histocompatibility complex binding assay and were able to induce hTERT-specific CTLs in both hTERT cDNA-immunized HLA-A*2402/Kb transgenic mice and patients with HCC. The CTLs were able to kill hepatoma cell lines depending on hTERT expression levels in an HLA-A*2402-restricted manner and induced irrespective of hepatitis viral infection. The number of single hTERT epitope-specific T cells detected by ELISPOT assay was 10 to 100 specific cells per 3 x 10(5) PBMCs, and positive T cell responses were observed in 6.9% to 12.5% of HCC patients. hTERT-specific T cell responses were observed even in the patients with early stages of HCC. The frequency of hTERT/tetramer+ CD8+ T cells in the tumor tissue of patients with HCC was quite high, and they were functional. In conclusion, these results suggest that hTERT is an attractive target for T-cell-based immunotherapy for HCC, and the identified hTERT epitopes may be valuable both for immunotherapy and for analyzing host immune responses to HCC.

Animals↗
PubMed2006

The development and clinical features of splenic aneurysm associated with liver cirrhosis.

OBJECTIVES: Splenic artery aneurysm (SAA) is usually asymptomatic, but can be fatal if it ruptures. Portal hypertensive patients with varix or splenomegaly are sometimes complicated by SAA. However, there have been no large-scale clinical studies regarding whether liver cirrhosis itself is associated with splenic aneurysm regardless of varix or splenomegaly. METHODS: In the present study, we retrospectively analyzed 303 cirrhotic patients examined with arteriography. The diagnosis and characteristics of SAAs were determined, and the relation with splenic artery diameter was evaluated. RESULTS: Nine patients (2.97%) had 12 complicated SAAs. The aneurysms, which measured 4-22 mm in diameter, were all saccular, and occurred commonly in the splenic hilum (50.0%). A correlation was noted between splenic artery diameter and aneurysm diameter (R(2)=0.706). Aneurysm growth was strongly associated with an increase in diameter of the splenic artery trunk (R(2)=0.705), which is closely related to arterial flow. CONCLUSIONS: SAA is considered a complication of cirrhosis. The increase in splenic artery diameter may result in SAA enlargement and rupture. Elective procedures should be considered based on the follow-up of main trunk or diameter of the splenic artery in addition to SAA size, a known risk factor of aneurysmal rupture.

Adult↗
PubMed2004

Nucleolin interacts with telomerase.

Telomerase is a specialized reverse transcriptase composed of core RNA and protein subunits which plays essential roles in maintaining telomeres in actively dividing cells. Recent work indicates that telomerase shuttles between subcellular compartments during assembly and in response to specific stimuli. In particular, telomerase colocalizes with nucleoli in normal human fibroblasts. Here, we show that nucleolin, a major nucleolar phosphoprotein, interacts with telomerase and alters its subcellular localization. Nucleolin binds the human telomerase reverse transcriptase subunit (hTERT) through interactions with its RNA binding domain 4 and carboxyl-terminal RGG domain, and this binding also involves the telomerase RNA subunit hTERC. The protein-protein interaction between nucleolin and hTERT is critical for the nucleolar localization of hTERT. These findings indicate that interaction of hTERT and nucleolin participates in the dynamic intracellular localization of telomerase complex.

Catalytic Domain↗
PubMed2002

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma.

Human telomerase reverse transcriptase, hTERT, is the catalytic component of human telomerase. Expression of hTERT confers telomerase activity, indicating that hTERT is the rate-limiting component of human telomerase. Here we report the detection of anti-hTERT auto-antibodies in the sera derived patients with hepatocellular carcinoma using recombinant, purified hTERT as an antigen in an enzyme linked immunosorbent assay (ELISA). The levels of anti-hTERT antibodies in serum correlated with progression to hepatocellular carcinoma. In contrast, we detected only low levels of anti-hTERT auto-antibodies in the sera derived from 18 normal volunteers. The observation of hTERT auto-antibodies in the sera derived from cancer patients suggests that such auto-antibodies constitute novel and specific tumor marker.

Adult↗
PubMed2001

Two independent regions of human telomerase reverse transcriptase are important for its oligomerization and telomerase activity.

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, contains motifs conserved among reverse transcriptases. Several nucleic acid-dependent polymerases that share a "fingers, palm, and thumb substructure" were shown to oligomerize. Here we demonstrate that hTERT also has this ability using partially purified recombinant hTERTs and mammalian cells co-expressing differently tagged hTERTs. Human template RNA (hTR), by contrast, has no effect on the structural oligomerization of hTERTs. Therefore, hTERT has an intrinsic ability of oligomerization in the absence of hTR. We identified two separate regions as essential for the oligomerization. The regions, amino acids 301-538 (amino-terminal region) and amino acids 914-928 (carboxyl-terminal region), are outside the fingers and palm substructure covering motif T to D and interact with each other in vivo. A substituted mutant of hTERT, hTERT-D712A-V713I, which was reported as a dominant negative form of hTERT, bound to the wild-type hTERT and inhibited its telomerase activity transiently expressed in telomerase-negative finite normal human fibroblast. The truncated forms of hTERT containing the binding region to the wild-type hTERT partially inhibited the telomerase activity, probably by preventing the wild-type hTERT from forming an oligomer. Taken together, the oligomerization of hTERT is an important step for telomerase activity.

Amino Acid Motifs↗