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Biomedical subjects

Tadashi Takahashi

Publications and source records attributed to Tadashi Takahashi.

8 recordsLinked to original sources

Enhanced gene targeting frequency in ku70 and ku80 disruption mutants of Aspergillus sojae and Aspergillus oryzae.

In the koji molds Aspergillus sojae and Aspergillus oryzae, exogenous DNA is integrated in the genome, in most cases irrespective of the sequence homology, suggesting that DNA integration occurs predominantly through a nonhomologous end joining pathway where two ku genes, namely, ku70 and ku80, play a key role. To determine the effect of ku gene disruption on the gene targeting frequency, we constructed ku70-, ku80-, and ku70-ku80-disrupted strains of A. sojae and A. oryzae. The gene targeting frequency of the tannase gene in ku70 and ku80 strains of both Aspergillus species was markedly enhanced as compared with that of the parental strains. The gene targeting frequency of the aflR and ku80 genes was also enhanced in an A. sojae ku70 background. Therefore, the koji mold strains with ku-disrupted genes will be excellent tools as hosts for efficient gene targeting.

Antigens, Nuclear↗

A quantitative near-infrared spectroscopy study: a decrease in cerebral hemoglobin oxygenation in Alzheimer's disease and mild cognitive impairment.

A newly developed quantitative near-infrared spectroscopy (NIRS) system was used to measure changes in cortical hemoglobin oxygenation during the Verbal Fluency Task in 32 healthy controls, 15 subjects with mild cognitive impairment (MCI), and 15 patients with Alzheimer's disease (AD). The amplitude of changes in the waveform, which was quantitatively calculated by a signal processing method, was significantly lower in the frontal, and the bilateral parietal areas in the AD group, whereas that in the MCI group was significantly lower only in the right parietal area. The NIRS system may be a potential tool for the primary screening of AD.

Alzheimer Disease↗

Identification and analysis of Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and Aspergillus oryzae.

Ku genes play a key role in the non-homologous end-joining pathway. We have identified Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and Aspergillus oryzae, and have constructed the disruption mutants of Ku70, Ku80, and Ku70-80 to characterize the phenotypic change in these mutants. Neither Ku70- nor Ku80-disrupted strains show hypersensitivity to the DNA damaging agents methylmethane sulfonate (MMS) and phleomycin. Moreover, undesirable phenotypes, such as poor growth or repressed conidiospore formation, were not observed in the Ku-disrupted A. sojae and A. oryzae.

Amino Acid Sequence↗

No genetic association between tumour necrosis factor receptor II 196R polymorphism and Japanese sporadic Alzheimer's disease.

Recent studies have reported that acute effects of tumour necrosis factor (TNF), a pro-inflammatory cytokine, are limited by binding to a soluble receptor, TNF receptor II, and the G allele at position 196 in exon 6 of the TNF receptor II gene (TNFRII 196R) has been associated with auto-immune diseases. Since complex interactions among cytokines have been suggested around senile plaques in Alzheimer's disease, TNF might be associated with ageing and the pathophysiology of Alzheimer's disease. We examined the TNFRII 196R polymorphism in 243 Japanese sporadic Alzheimer's disease cases and 106 control cases using a polymerase chain reaction-restriction fragment length polymorphism method. Allelic frequencies with TNFRII 196R T/G polymorphism were 28.3% and 27.4% in the control and Alzheimer's disease groups, respectively. The results showed no genetic association between TNFRII 196R polymorphism and Alzheimer's disease. The TNFRII 196R G allele does not appear to be associated with Alzheimer's disease susceptibility in a Japanese population.

Adult↗

Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases.

Interleukin-6 (IL-6), an inflammatory cytokine might be involved in the pathophysiology of Alzheimer disease (AD); several studies have reported that the "C allele of IL-6 variable number of tandem repeat polymorphism" (IL-6vntr) delayed initial onset of AD and also decreased its risk per se. Another polymorphism, G/C allele of IL-6 gene promoter region (IL-6prom), is also a candidate because it has an influence on the regulation of plasma IL-6 concentration. We examined these IL-6 polymorphisms in 128 Japanese AD cases and 83 control cases using a PCR-RFLP method. The results showed the frequency of the IL-6prom G allele was significantly increased in AD, although IL-6vntr polymorphism was not. Plasma IL-6 concentration of the AD cases was also significantly higher than that of the control cases. Moreover, the IL-6prom G allele-positive AD patients showed a tendency to have higher IL-6 concentration in the AD group. These findings suggest that the IL-6prom G allele which may affect plasma IL-6 concentration might be a risk factor for sporadic AD in Japanese.

Aged↗

The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's disease.

Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the inflammation pathology observed surrounding senile plaques, and may also associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been reported that a single nucleotide polymorphism in the IL4 gene promoter region, IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD. In the present study, therefore, we investigated this mutation in 108 healthy controls and in 178 sporadic AD cases by the polymerase chain reaction restriction fragment length polymorphism method in a Japanese AD population. Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD. We also tested whether the IL4 functional variants were regulated by this polymorphism in a portion of the subjects (16 AD cases and 13 control cases). We could not find any relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.

Adult↗

Effects of dietary consistency on the mandible of rats at the growth stage: computed X-ray densitometric and cephalometric analysis.

Thirty 3-week-old male Wistar rats were grouped into a hard diet control group, a kneaded-diet group, and a powdered-diet group. After 6 weeks of growth, all rats were killed under deep anesthesia. The effects of dietary physical consistency on the mandible were investigated with respect to morphology and bone mineral content using lateral cephalometric analysis and computed X-ray densitometry. Significant differences between the experimental and control groups were determined by measuring the means and standard deviation of the coordinates and differences between 15 points selected on the mandibles. Gonion (Go), which is a measurement of depth to the X-axis, was significantly less in the powdered-diet group, while the kneaded-diet group showed no significant differences. The most posterior point of the coronoid process (Cr) and the most posterior point of condylar process (Cd), which are measures of height to the Y-axis, were less in the kneaded-diet group than in the control group. In the powdered-diet group, Cr, Cd, Go and Infradentale were significantly less than in the control group. On the other hand, the bone mineral content was significantly lower in the coronoid process and angle of mandible in only the powdered-diet group.

Absorptiometry, Photon↗

Nonfunctionality of Aspergillus sojae aflR in a strain of Aspergillus parasiticus with a disrupted aflR gene.

Aspergillus sojae belongs to the Aspergillus section Flavi but does not produce aflatoxins. The functionality of the A. sojae aflR gene (aflRs) was examined by transforming it into an DeltaaflR strain of A. parasiticus, derived from a nitrate-nonutilizing, versicolorin A (VERA)-accumulating strain. The A. parasiticus aflR gene (aflRp) transformants produced VERA, but the aflRs transformants did not. Even when aflRs was placed under the control of the amylase gene (amyB) promoter of Aspergillus oryzae, the amy(p)::aflRs transformants did not produce VERA. A chimeric construct containing the aflRs promoter plus the aflRs N- and aflRp C-terminal coding regions could restore VERA production, but a construct containing the aflRp promoter plus the aflRp N- and aflRs C-terminal coding regions could not. These results show that the A. sojae aflR promoter is functional in A. parasiticus and that the HAHA motif does not affect the function of the resulting hybrid AflR. We conclude that the lack of aflatoxin production by A. sojae can be attributed, at least partially, to the premature termination defect in aflRs, which deletes the C-terminal transcription activation domain that is critical for the expression of aflatoxin biosynthetic genes.

Amylases↗