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Biomedical subjects

K Akagi

Publications and source records attributed to K Akagi.

At least 19 recordsLinked to original sources

One-dimensional transport in polymer nanofibers.

We report our transport studies in quasi-one-dimensional (1D) conductors-helical polyacetylene fibers doped with iodine-and the data analysis for other polymer single fibers and tubes. We found that at 30 K<T<300 K, the conductance and the current-voltage characteristics follow the power law G(T) proportional, Talpha with alpha approximately 2.2-7.2 and I(V) proportional, Vbeta with beta approximately 2-5.7. Both G(T) andI(V) show the features characteristic of 1D systems such as a Luttinger liquid or Wigner crystal. The relationship between our results and theories for tunneling in 1D systems is discussed.

Journal Article↗

MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes.

AML1-MTG8 chimeric oncogene is generated in acute myelogenous leukemia with t(8;21), and seems to be responsible for the pathogenesis of the disease. However, the role of MTG8 is ambiguous. Here we found that MTG8 interacted with the regulatory subunit of type II cyclic AMP-dependent protein kinase (PKA RIIalpha). The binding site of MTG8 was NHR3 domain, and that of RIIalpha was the N-terminus for interacting with PKA anchoring proteins (AKAPs). NHR3 contains a putative alpha-amphipathic helix which is characteristic in binding of AKAPs with RII. Indirect immunofluorescence microscopy showed that MTG8 and RIIalpha were overlapped at the centrosome-Golgi area in lymphocytes. These findings suggest that MTG8 may function as an AKAP at the centrosome-Golgi area in lymphocytes.

Amino Acid Sequence↗

Green tea catechins enhance tumor development in the colon without effects in the lung or thyroid after pretreatment with 1,2-Dimethylhydrazine or 2,2'-dihydroxy-di-n-propylnitrosamine in male F344 rats.

Modifying effects of green tea catechins (GTCs) on the post-initiation stage of colon, lung and thyroid carcinogenesis were examined in F344 male rats. Groups of 20 animals were given subcutaneous injections of 40 mg/kg body wt of 1,2-dimethylhydrazine twice a week for 2 weeks or oral administration of 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) in the drinking water for 2 weeks for initiation. They then received diet containing 1 or 0.1% green tea catechin or basal diet alone for 33 weeks. Histopathological examination after final sacrifice showed that although total incidence and multiplicity of colon tumors were not significantly different from controls, values for colon adenomas were decreased while those for carcinomas and the average size of tumors were significantly increased in the 0.1% GTC group. A similar tendency was observed for the 1% GTC group. Incidences and/or multiplicity of lung hyperplasia and tumors, and thyroid lesions did not significantly vary among the DHPN-treated groups. These results indicate that GTCs do not inhibit, but rather may enhance colon carcinogenesis, while not influencing lung and thyroid carcinogenesis under the present experimental conditions.

1,2-Dimethylhydrazine↗

Reconstitution of acid secretion in digitonin-permeabilized rabbit gastric glands. Identification of cytosolic regulatory factors.

When isolated rabbit gastric glands were permeabilized with digitonin, they lost their ability to secrete acid, as monitored by [14C]aminopyrine accumulation, and they never recovered by supplement with cytosol prepared from gastric mucosa. However, the permeabilized glands elicited acid secretion when brain cytosol was supplemented. Fractionation of gastric cytosol by gel filtration revealed that the fraction at 30 kDa stimulated permeabilized glands by itself, whereas the 200-kDa fraction potently inhibited brain cytosol-stimulated acid secretion. Brain cytosol contained only the former stimulatory factor. With further gel filtration, the 30-kDa activator was separated into two components, 20 kDa (peak 1) and 1.8 kDa (peak 2), both of which are necessary for full activity. We purified peak 1 from bovine brain, and phosphatidylinositol transfer protein (PITP) was identified as the main component of the activity. The stimulating activity in brain and gastric mucosa correlated with the contents of PITP, and recombinant PITP mimicked the effect of peak 1, suggesting that PITP is one of the essential components in gastric acid secretion. When gastric glands were stimulated, the inhibitory activity, but not stimulatory activity, in the cytosol was increased. This suggests a regulatory mechanism such as stimulation translocates the inhibitory component from the secretory site on the membrane to cytosol. These results demonstrate a high degree of usefulness for our present model, the reconstituted digitonin-permeabilized gastric glands.

Animals↗

A novel tetracycline-dependent transactivator with E2F4 transcriptional activation domain.

A tetracycline-controlled gene expression system provides a powerful tool to dissect the functions of gene products. However, it often appears difficult to establish cell lines or transgenic animals stably expressing tetracycline-dependent transactivators, possibly as a result of toxicity of the transactivator domains used. In order to overcome this problem, we developed a novel tetracycline-dependent transactivator that works efficiently in mammalian cells. This transactivator is a fusion of the tet reverse repressor mutant and the transcriptional activating domain of human E2F4, which is ubiquitously expressed in vivo. We demonstrate here that this tetracycline-regulated gene expression system provides a two log transcriptional activation in mammalian cells as assessed by northern blot and luciferase analyses. Combining this system with green fluorescent protein reporter systems or microarray gene expression profiling will facilitate the study of gene function.

Animals↗

Vertex epidural hematoma associated with traumatic arteriovenous fistula of the middle meningeal artery: a case report.

BACKGROUND: Vertex epidural hematomas are rare. We describe the features of a vertex epidural hematoma associated with an arteriovenous fistula (AVF) of the meningeal artery created by a laceration of the dura mater underlying a linear skull fracture. Although AVF associated with convexity epidural hematomas has been reported, we know of no such previous report of vertex epidural hematomas. CASE DESCRIPTION: A 65-year-old woman presented with generalized headache following head injury. On hospital day 3, she developed a left hemiparesis. Magnetic resonance imaging (MRI) disclosed a thick epidural hematoma at the vertex. Cerebral angiography showed an AVF between the middle meningeal artery and a venous lake. On hospital day 4, the epidural hematoma was evacuated. CONCLUSION: Although coronal MRI was important for diagnosis of this vertex epidural hematomas, the case particularly illustrates the importance of cerebral angiography. The delayed onset of hemiparesis most likely reflected a continuing increase in hematoma volume because of bleeding from the lacerated meningeal artery.

Aged↗

Germline mutation of dihydropyrimidine dehydrogenese gene among a Japanese population in relation to toxicity to 5-Fluorouracil.

5-Fluorouracil (5FU) is most commonly used in chemotherapy for human malignancy. Over 80% of administered 5FU is metabolically degraded by dihydropyrimidine dehydrogenase (DPD), a primary and rate-limiting enzyme in the 5FU metabolic pathway. A DPD-deficient phenotype among cancer patients, which has posed a serious problem in 5FU-based chemotherapy, was reported to be in part ascribed to germline mutations in dihydropyrimidine dehydrogenase (DPYD) gene. Therefore, we for the first time examined the frequencies and types of germline mutations in the DPYD gene among a total of 107 Japanese cancer patients and healthy volunteers. Of 214 alleles examined among them, 181 alleles were of the same type, which was assigned as wild type; 21 alleles revealed a nucleotide substitution resulting in silent mutation; and the remaining 12 alleles showed five types of nucleotide deletion or substitutions resulting in one frameshift and four missense mutations. Three of them, A74G, 812delT and L572V, were novel mutations. None of the study subjects showed homozygous frameshift or missense mutated alleles. We also studied the association between toxic response to 5FU and heterozygous frame shift or missense mutation of the DPYD gene among eight cancer patients who had received 5FU-based chemotherapy. These patients did not show any adverse effects higher than grade 3, suggesting that heterozygotes are not associated with increased toxicity to 5FU. Our results indicate that a very small percentage, about 0.2%, of the Japanese population seems to carry homozygous mutations in DPYD gene, mutations which possibly indicate genetically increased toxicity of 5FU-based chemotherapy.

Antimetabolites, Antineoplastic↗

Strain-dependency of chromosomal abnormalities in lymphomas developed in E mu-myc transgenic mice.

We previously showed that B and T cell lymphoma development in Em (immunoglobulin heavy chain enhancer)-myc transgenic mice is dependent on the mouse strain. To determine whether any non-random chromosomal abnormality that was present was caused by variations in the lymphoma cell type or by a different genetic background, we crossed C3H transgenic mice with other inbred strains of mice, C57BL / 6 or BALB / c. Cytogenetic analysis showed a high frequency of non-random chromosomal aberrations, namely, duplication or amplification of part of chromosome 5 containing the transgene and trisomy of chromosome 1, 6, or 12 in the genetic background of C3H x C57BL / 6 mouse and C3H x BALB / c mouse, respectively, regardless of cell type of lymphoma. These results suggest that non-random chromosomal abnormalities in lymphoma cells are dependent on the genetic background of mouse, not on the tumor cell type in Em-myc transgenic mouse.

Animals↗

Acute phase response in toxicity studies. I. Survey of beagle dogs subjected to single-dose toxicity studies.

In the field of routine single-dose toxicity studies, we occasionally meet with transient leukocytosis associated with an increase in fibrinogen in beagle dogs within a few days after treatment with the test article. Only a little is known, however, about the toxicological significance of these changes. However, these changes were thought to belong to the category of "Acute Phase Response, APR," which has been known for a long time in connection with injury, trauma or infection. Aiming at proper understanding of these experiences, we surveyed 25 single-dose toxicity studies (7 intravenous bolus, 5 intravenous infusion, 12 oral and 1 subcutaneous treatment, hereafter referred to simply as i.v. bolus, i.v. infusion, oral and s.c.) in beagle dogs, provided with data from hematological examinations. We set the following criteria as a positive response in the present survey: increases of 50% or more in either or both WBC or fibrinogen compared to the predosing value, transiently from Day 1 to Day 3 of the study. Among 25 studies surveyed, about 1/2 of the studies exhibited increases of 50% or more in either or both fibrinogen or WBC counts compared to the predosing values showing dose-dependency transiently on Day 1 or Day 2. These changes were remarkable after intravenous application. Oral application produced similar effects, although the incidence and severity were low compared to the i.v. routes. Regarding blood chemical and hematological changes other than changes in fibrinogen and WBC counts, there were no essential differences between the groups of studies with and without the changes in fibrinogen and WBC counts. These changes were thought to be characteristic and to have occurred as incidents unrelated to other changes. The reported changes seen in single-dose toxicity studies may belong to the category of APR as the non-specific mechanism of living bodies as stated by Burns et al. (1996).

Acute-Phase Reaction↗

Cosmetic and functional reconstruction achieved using a split myofascial bone flap for pterional craniotomy. Technical note.

Cosmetic deformities that appear following pterional craniotomy are usually caused by temporal muscle atrophy, injury to the frontotemporal branch of the facial nerve, or bone pits in the craniotomy line. To resolve these problems during pterional craniotomy, an alternative method was developed in which a split myofascial bone flap and a free bone flap are used. The authors have used this method in the treatment of 40 patients over the last 3 years. Excellent cosmetic and functional results have been obtained. This method can provide wide exposure similar to that achieved using Yaşargil's interfascial pterional craniotomy, without limiting the operative field with a bulky temporal muscle flap.

Bone and Bones↗

Cerebral aneurysm associated with an anomalous hyperplastic anterior choroidal artery.

An unruptured internal carotid artery (ICA) aneurysm arising at the origin of a hyperplastic anomalous AchoA was identified together with a second unruptured middle cerebral artery aneurysm during angiography performed to investigate a striatal and intraventricular haemorrhage in a 55-years-old woman. The anomalous hyperplastic AchoA supplied the left temporal and occipital lobes, and the aneurysm arose proximal to its origin. The patient underwent clipping of the aneurysms, and intra-operative observation revealed that several perforating branches arose directly from the ICA between the AchoA and the ICA bifurcation.

Carotid Artery Diseases↗

Ribonuclease H attack of leukaemic fused transcripts AML1-MTG8 (ETO) by DNA/RNA chimeric hammerhead ribozymes.

BACKGROUND: Catalytic anti-sense oligonucleotides might be useful tools for controlling specific gene expression. However, to obtain effective oligonucleotides of the desired function in vivo is still a difficult task. RESULTS: To evaluate the usefulness of synthesized DNA/RNA hammerhead ribozymes targeting AML1-MTG8 (ETO) leukaemic fusion transcripts in vivo, we analysed their effects on cell growth and the mechanism of action using isolated cell nuclei. These ribozymes inhibited the growth of leukaemic cell lines expressing the AML1 -MTG8 and degraded AML1-MTG8 mRNA in isolated nuclei of these cells. However, the reactions gave rise to additional cleavage products. Systematic cleavage analyses using an anti-sense oligonucleotide array revealed that the cleavage was induced by endogenous RNase H at specific sites, in accordance with their calculated melting temperature (Tm) values. With suppression of RNase H by sulfhydryl agents, the DNA/RNA ribozyme had a ribozyme catalytic activity. In addition, the ribozymes and anti-sense oligonucleotides suppressed the AML1-MTG8 protein in the leukaemic cells. CONCLUSIONS: The DNA/RNA ribozymes inhibited cell growth primarily via anti-sense effects, the main role of which was the activation of RNase H-digestion by their DNA arms. In addition, the isolated nuclei provided a useful assay system for modelling in vivo conditions for the quantitative evaluation of anti-sense/ribozyme activity.

Antisense Elements (Genetics)↗

Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues.

Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce lymphangiogenesis. We examined the relationship between expression of VEGF-C and clinicopathological features in patients with colorectal cancer. The expression of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal cancer patients was examined immunohistochemically. To verify VEGF-C mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes metastasis, and depth of invasion. On the other hand, correlations were nil with regard to gender of the patients, histologic type, venous involvement, and liver metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly consistent with this expression in the primary tumour. Survival time was shorter for VEGF-C positive groups than for VEGF-C negative ones, but with no statistically significant difference. RT-PCR findings revealed that the expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein expression. VEGF-C may play an important role in lymphatic spread of colorectal cancer.

Adolescent↗

Differences between features of adenoma in the rectum versus sigmoid colon.

OBJECTIVE: Although the prevalence of cancer in the rectosigmoid is high compared with that in the more proximal colon, the features of cancer developing from an adenoma have yet to be elucidated. The aim of this study is to examine the clinicopathological relationship between cancer and adenoma in the rectosigmoid. METHODS: A total of 340 adenomas located in the rectosigmoid in 255 patients were retrospectively examined regarding such clinicopathological factors as location and the grade of dysplasia. RESULTS: The prevalence of adenoma was 102 in the rectum and 238 in the sigmoid colon, respectively, whereas the prevalence of adenoma with high-grade dysplasia was 39 in the rectum and 48 in the sigmoid colon, respectively. This prevalence of adenoma with high-grade dysplasia was thus significantly higher in the rectum than in the sigmoid colon (p < 0.02). CONCLUSIONS: These findings suggest the possibility of different types of cancer development between adenoma of the rectum and sigmoid colon.

Adenocarcinoma↗