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Biomedical subjects

Kazuo Tanaka

Publications and source records attributed to Kazuo Tanaka.

At least 19 recordsLinked to original sources

Public-key system using DNA as a one-way function for key distribution.

Novel public-key system using DNA has been developed. To solve key distribution problem, the public-key cryptography system based on the one-way function has been developed. The message-encoded DNA hidden in dummies can be restored by PCR amplification, followed by sequencing. We used these operations as a one-way function, and constituted a novel method for the key distribution based on the public-key system using DNA. We will show the way of holding a key in common just between specific two persons.

Base Sequence↗

Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment.

BACKGROUND: We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy. METHODS: We initially studied 141 patients treated with lamivudine for 1 year or more, and 49 patients who showed viral breakthrough were the subjects of this study. Their mean lamivudine administration period was 2.3 +/- 0.9 years. RESULTS: After viral breakthrough, breakthrough hepatitis occurred in 47 patients (95.9%), but did not occur in the other 2 (4.1%). Four of the 47 patients with breakthrough hepatitis were observed without further treatment, and the alanine transferase (ALT) level was normalized in 2 of them but fluctuated in the other 2. Breakthrough hepatitis was treated by injection of glycyrrhizin or ursodeoxycholic acid administration in 36 of the remaining 43 patients, and by antiviral drug administration in the other 7 (entecavir in 2 patients, adefovir in 2, and interferon in 3). The ALT level was normalized in 5 of the 36 patients treated with glycyrrhizin or ursodeoxycholic acid, but persistently fluctuated in the other 31. In those with normalized ALT after the occurrence of breakthrough hepatitis, the peak ALT level at that point was significantly lower (86 +/- 47 IU/l) than that in the patients without normalization (206 +/- 167 IU/l). CONCLUSIONS: These results showed that there were a few patients who did not develop breakthrough hepatitis after showing viral breakthrough, and some who showed normalization of the ALT level after the occurrence of breakthrough hepatitis, but in many patients, ALT continuously fluctuated.

Administration, Oral↗

Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area: a pilot study.

Hepatitis C virus (HCV) infection may contribute to the development of type 2 diabetes mellitus. However, this association at the population level remains unclear. The aim of this pilot study is to examine the relationship between HCV infection and the development of type 2 diabetes mellitus in an HCV hyperendemic area where we conducted health screenings in 1995. After 7 years of follow-up, we evaluated the relative risk of the development of type 2 diabetes mellitus in anti-HCV-inhabitants. Among 71 subjects free of diabetes mellitus in 1995, 7 developed type 2 diabetes mellitus during the 7-year follow-up evaluation. Overall, anti-HCV-positive subjects were nearly 3-fold as likely as anti-HCV-negative subjects to develop diabetes mellitus, but this difference was not statistically significant (p=0.08). After stratification of the anti-HCV-positive group according to serum HCV core titer, a significant increase in the incidence of diabetes was seen in subjects with high titer of HCV core compared to anti-HCV-negative subjects (p=0.02; relative hazard, 5.60; 95% confidence interval, 1.41 to 37.42). In conclusion, HCV infection potentially has a significant role in the development of type 2 diabetes mellitus at the population level. Further large-scale studies are needed to confirm these preliminary findings.

Diabetes Mellitus, Type 2↗

Extrahepatic manifestations and insulin resistance in an HCV hyperendemic area.

Hepatitis C virus (HCV) causes extrahepatic manifestations as well as liver diseases, and contributes to insulin resistance and type 2 diabetes mellitus. The purpose of the present study was to evaluate the relationship of extrahepatic manifestations and insulin resistance in an HCV hyperendemic area. We investigated the incidence of extrahepatic manifestations among 139 inhabitants living in an HCV hyperendemic area in 2002 and compared it to 1999 data for the same inhabitants. Insulin resistance was tested for some non-HCV or HCV-infected inhabitants we had identified during mass screenings in 1999 and 2002. For some of the inhabitants in 2002, we examined records on the prevalence of insulin resistance seven years earlier. The prevalence of extrahepatic manifestations among individuals with positivity for anti-HCV antibodies was higher than among those without HCV in both 1999 and 2002. The prevalence of each extrahepatic manifestation which we identified in 2002 was higher than in 1999. Moreover, in some non-HCV or HCV-infected inhabitants, insulin resistance in 2002 was significantly higher than in 1999. Among inhabitants who had HCV infection with extrahepatic manifestations, fasting insulin levels or HOMA-IR findings seven years prior was significantly higher than for inhabitants who had neither HCV infection nor extrahepatic manifestations (p = 0.03, p = 0.01, respectively). Insulin resistance induces HCV infection, which causes an increase in the incidence of extrahepatic manifestations in HCV-infected individuals.

Aged↗

Photostimulated hole transport through a DNA duplex immobilized on a gold electrode.

Photostimulated hole transport through DNA duplexes immobilized on gold electrodes has been investigated. By modifying a gold electrode with a DNA duplex containing a photosensitizer, we have observed a sequence-dependent cathodic photocurrent. DNA acts as a good mediator for cathodic photocurrent when appropriate sequences are selected.

Anthraquinones↗

Synthesis of an artificial hole-transporting nucleoside triphosphate, dMDATP, and its enzymatic incorporation into DNA.

We report on the enzymatic synthesis of DNA wires by successive incorporation of artificial nucleotides. We synthesized an efficient hole-transporting nucleoside triphosphate, d(MD)ATP, and have examined the screening of polymerases and reverse transcriptases for enzymatic incorporation of d(MD)ATP into DNA. We found that KOD Dash is an effective enzyme for the enzymatic synthesis of (MD)A-containing DNA. Furthermore, the efficiency of enzymatic incorporation was remarkably improved by the addition of manganese chloride. By applying the PCR method to the synthesis of DNA containing a run of (MD)A, the (MD)A run was amplified up to 6 x 10(6) times. (MD)A runs prepared by the enzymatic method exhibited a high hole-transporting ability.

Adenosine Triphosphate↗

DNA logic gates.

A conceptually new logic gate based on DNA has been devised. Methoxybenzodeazaadenine ((MD)A), an artificial nucleobase which we recently developed for efficient hole transport through DNA, formed stable base pairs with T and C. However, a reasonable hole-transport efficiency was observed in the reaction for the duplex containing an (MD)A/T base pair, whereas the hole transport was strongly suppressed in the reaction using a duplex where the base opposite (MD)A was replaced by C. The influence of complementary pyrimidines on the efficiency of hole transport through (MD)A was quite contrary to the selectivity observed for hole transport through G. The orthogonality of the modulation of these hole-transport properties by complementary pyrimidine bases is promising for the design of a new molecular logic gate. The logic gate system was executed by hole transport through short DNA duplexes, which consisted of the "logic gate strand", containing hole-transporting nucleobases, and the "input strand", containing pyrimidines which modulate the hole-transport efficiency of logic bases. A logic gate strand containing multiple (MD)A bases in series provided the basis for a sharp AND logic action. On the other hand, for OR logic and combinational logic, conversion of Boolean expressions to standard sum-of-product (SOP) expressions was indispensable. Three logic gate strands were designed for OR logic according to each product term in the standard SOP expression of OR logic. The hole-transport efficiency observed for the mixed sample of logic gate strands exhibited an OR logic behavior. This approach is generally applicable to the design of other complicated combinational logic circuits such as the full-adder.

Base Sequence↗

Cytosine detection by a fluorescein-labeled probe containing base-discriminating fluorescent nucleobase.

We report on a new method for the detection of a base at a specific site in a DNA sequence by monitoring the fluorescence emission of fluorescein. To achieve this goal, we developed a new base-discriminating fluorescent (BDF) nucleobase, naphthodeazaadenine ((ND)A). The fluorescence spectrum of the duplex possessing a cytosine base as a complementary base of (ND)A showed a fluorescence peak at 383 nm when using an excitation wavelength of 350 nm. When the complementary base of (ND)A was one of the other bases, the fluorescence intensity was very low. The fluorescence emission spectrum of (ND)A overlapped with the fluorescence excitation spectrum of fluorescein in the wavelength range of 400-500 nm. Thus, we designed FRET-BDF probes containing (ND)A as the FRET donor and fluorescein as the acceptor. The interaction of these two fluorophores, which are separated by defined base pairs, allowed an efficient energy transfer that resulted in a dominant fluorescence emission of fluorescein at 520 nm when using an excitation wavelength of 350 nm. Fluorescence emission from FRET-BDF probes was observed only when the complementary base of (ND)A is C, thus achieving a clear distinction of a C base on the complementary DNA strand. However, the general utility of our method is limited due to the quenching of the (ND)A fluorescence by a G/C base pair flanking (ND)A.

Base Pairing↗

Analysis and numerical computation of diffraction of an optical field by a subwavelength-size aperture in a thick metallic screen by use of a volume integral equation.

Diffraction of an optical field by an aperture in a thick metallic screen is analyzed numerically by use of a three-dimensional volume integral equation together with a generalized conjugate residual method and fast Fourier transformation. Numerical results were validated by reciprocity and the independence of the results of the truncated discretized volume size used in numerical calculations. Near and far fields of square, circular, and triangular apertures in a thick screen are obtained numerically. Some of the numerical results obtained in the present study agree with previously reported experimental results. The surface plasmon polaritons excited on the sidewalls of the aperture can explain the basic characteristics of near-field distribution of apertures. The Bethe-Bouwkamp theory was found to be insufficient to explain the basic characteristics of the near field around the subwavelength aperture in a practical metallic screen.

Journal Article↗

A nucleobase that releases reporter tags upon DNA oxidation.

We have developed a novel nucleosbase, edaG, that efficiently releases various reporter units upon one-electron oxidation. The edaG-selective degradation of ODNs was achieved by various mild oxidizing agents. The oxidant-dependent molecular releasing technique is quite useful not only for DNA-based drug releasing systems but also for the detection of long-range hole transport through DNA without time-consuming analysis.

Biosensing Techniques↗

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy.

It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV.

Adult↗

Analysis of approach to therapy for chronic liver disease in an HCV hyperendemic area of Japan.

In 1990, we conducted an epidemiological study of 509 residents in a hepatitis C virus (HCV) hyperendemic area in Japan. The purpose of the present study was to examine the approach to therapy for liver diseases accompanied by HCV and hepatitis B virus (HBV) infections among the surviving residents in the town after 12 years. Fifty-three with HCV or HBV infections among 385 people who resided in the town were clearly analyzed in 2002. The number of persons diagnosed with the liver diseases was as follows: HCV-related asymptomatic healthy carrier (1), past history of HCV infection (15), chronic hepatitis C (22), HCV-related liver cirrhosis (6), HCV-related hepatocellular carcinoma (HCC) (5), and HBV-related asymptomatic healthy carrier (4). HCC was detected in residents who did not have periodic regular hospital checkups. Only 19% of the 53 inhabitants consulted liver medical specialists, and 75% (3/4) who received interferon therapy received treatment from a liver medical specialist. It is necessary to provide continuous medical treatment to HCV carriers, minimizing difference in treatment quality in different medical institution. An efficient HCV medical checkup and a program of subsequence health management are important problems to be solved for improved health care.

Journal Article↗

Simulation of confined and enhanced optical near fields for a long narrow aperture in a pyramidal structure on a thick metallic screen.

A new type of long narrow aperture in a pyramidal structure on a thick metallic screen is proposed, and optical wave scattering by this structure is simulated. This aperture structure provides high emission intensity and small spot size simultaneously through excitation of the surface plasmon polaritons on the sidewalls of the pyramidal structure. Scattering of optical waves by this structure in the thick metallic screen is solved numerically with a volume integral equation by generalized conjugate residual iteration and fast Fourier transformation. The basic characteristics of the near-field intensities of the aperture are investigated in detail.

Journal Article↗

Design of base-discriminating fluorescent nucleoside and its application to t/c SNP typing.

We report a novel method for base detection using a base-discriminating fluorescent (BDF) nucleoside. We developed BDF probes containing methoxybenzodeazaadenine MDA and methoxybenzodeazainosine MDI, which give strong fluorescence only when the base on the complementary strand is cytosine and thymine, respectively. Thus, the MDA- and MDI-containing ODNs can be used as a very effective BDF probe for the detection of single base alterations, such as SNPs and point mutations. The present method using BDF probes is a very powerful tool for SNP typing that does not require any enzymes and time-consuming steps, and can avoid hybridization errors. In addition, a combination of MDA- and MDI-containing BDF probes facilitates the T/C SNP typing of a heterozygous sample.

Adenine↗

Rational design of a DNA wire possessing an extremely high hole transport ability.

DNA is a promising conductive biopolymer. However, there are problems that need to be solved to realize real DNA wires. These include the low efficiency of hole transport and the serious oxidative damage that can occur during hole transport. We have demonstrated a protocol for the design of a DNA wire that can effectively mediate hole transport that is not adversely affected by oxidation during hole transport through the DNA duplex. We have synthesized a stable and effective DNA wire by incorporating a designer nucleobase, benzodeazaadenine derivatives, which have lower oxidation potentials and wider stacking areas but are not decomposed during hole transport.

Adenine↗