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Biomedical subjects

S Otsuka

Publications and source records attributed to S Otsuka.

At least 19 recordsLinked to original sources

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗

A proposal for the unification of five species of the cyanobacterial genus Microcystis Kützing ex Lemmermann 1907 under the rules of the Bacteriological Code.

Genomic DNA homologies were examined from six Microcystis (cyanobacteria) strains, including five different species, Microcystis aeruginosa, Microcystis ichthyoblabe, Microcystis novacekii, Microcystis viridis and Microcystis wesenbergii. All DNA-DNA reassociation values between two strains of M. aeruginosa and the other four species exceeded 70%, which is considered high enough for them to be classified within the same bacterial species. It is proposed to unify these five species into M. aeruginosa under the Rules of the Bacteriological Code and NIES843T (= IAM M-247T) is proposed as the type strain. Two other species, Microcystis flos-aquae and Microcystis pseudofilamentosa, should be regarded as morphological variations of this unified M. aeruginosa. The current taxonomy of cyanobacteria depends too much upon morphological characteristics and must be reviewed by means of bacteriological methods as well as traditional botanical methods.

DNA, Bacterial↗

Correlation between diffuse pigmentation and keratinocyte-derived endothelin-1 in systemic sclerosis.

BACKGROUND: The precise mechanism of diffuse pigmentation in systemic sclerosis (SSc) is still unknown. We suspected the participation of endothelin-1 (ET-1), which is produced by keratinocytes, in the hyperpigmentation in SSc. The aims of this study are to demonstrate the hyperproductivity of ET-1 from epidermal cells in SSc by in situ hybridization histochemistry, and to show a correlation between the hyperproductivity of ET-1 in keratinocytes and skin hyperpigmentation. METHODS: In situ hybridization histochemistry was performed on nine SSc specimens (five cases of diffuse scleroderma (dSSc), four cases of acrosclerosis (lSSc)), and compared with four normal control specimens. We counted the grains on 10 x 10 microm(2) of epidermis and microvessels in each histology and examined the degree of skin pigmentation using the skin reflectance factor (Y). RESULTS: In the specimens of the SSc patients, the number of grains on the epidermis was remarkably higher than those of the control specimens (P < 0.01). We found a close correlation between the number of grains and the skin reflectance factor in dSSc patients (P = 0.02). Correlations were not identified between serum ET-1 and skin pigmentation and between serum ET-1 and the frequency of grains on the epidermis. As for grains on microvessels, lSSc patients showed a greater frequency than dSSc patients. CONCLUSIONS: The findings of this study suggest that an increase in the ET-1 productivity of keratinocytes is experienced in SSc patients, especially in dSSc patients. The results suggest a strong correlation between the ET-1 productivity of keratinocytes and skin pigmentation in severe cases of SSc. We conclude from these results that keratinocyte-derived ET-1 plays an important role in the pathogenesis of the hyperpigmentation of the skin in SSc patients.

Adult↗

Extensive cell death in thymocytes in colon 26-induced cachectic mice.

Extensive atrophy has been reported to occur in the thymus in a cancer-burden state but the mechanisms of this atrophy have not been fully elucidated. We investigated changes in the thymus in tumour-bearing mice inoculated with two subclones of the murine colon 26 adenocarcinoma cell line: clone 5 (non-cachectic) and clone 20 (cachectic). In clone 20 mice, body weights and thymocyte numbers decreased significantly compared with controls. Flow cytometric analysis of the thymocytes demonstrated that the frequency of single positive cells (CD4+ CD8- and CD4- CD8+) was significantly increased and that of double positive cells (CD4+ CD8+) was significantly decreased in clone 20 mice and, to a lesser extent, in clone 5 mice compared with controls. Serum levels of interleukin 6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly elevated. These results suggested that thymocyte apoptosis was accelerated in the cancer-cachectic state, and increased GM-CSF might be partly responsible for thymic atrophy.

Adenocarcinoma↗

Phylogenetic relationships between toxic and non-toxic strains of the genus Microcystis based on 16S to 23S internal transcribed spacer sequence.

16S to 23S ribosomal DNA internal transcribed spacer sequences of 47 strains of the genus Microcystis were determined. Derived maximum likelihood and DNA distance trees indicated that Microcystis can be divided into three clusters. The first cluster included toxic and non-toxic strains, the second only toxic ones, and the third only non-toxic ones. The tree topologies were not necessarily correlated with morphospecies distinction or phycobilin pigment composition, and one genotype may have more than one morphotype. Phylogenetic analysis based on intergenic spacer sequences was thought to be effective for understanding relationships among closely related species and strains.

Base Sequence↗

Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma.

BACKGROUND: In primary hyperparathyroidism, certain genetic abnormalities responsible for parathyroid tumorigenesis are proposed, and it has been reported that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the parathyroid hormone (PTH) gene is one of the genetic disorders in a number of primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by uremia, the mechanism of monoclonal proliferation in nodular parathyroid hyperplasia is not well understood. To elucidate the mechanism, we examined the expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary adenoma and secondary hyperplasia. METHODS: In adenomas (N = 15) and associated glands (N = 7) with normal histology obtained from patients with primary hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single nodular (N = 28) glands from patients who underwent parathyroidectomy for renal hyperparathyroidism, the expression of these cell cycle regulators was evaluated by immunohistochemical technique. A labeling index was used to define the proportion of cells with positive nuclear staining by each antibody. RESULTS: In 6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling index of more than 500), possibly because of the PTH gene rearrangement, but not in secondary hyperplasia, including single nodular glands. Compared with diffuse hyperplasia, nodular hyperplasia showed a significantly higher expression of PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P < 0.05). However, no statistically significant correlation between the expression of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and secondary hyperplasia. CONCLUSIONS: These results suggest that in secondary hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin D1 induced by PTH gene rearrangement may be not the major genetic abnormality responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to monoclonal proliferation of parathyroid cells induced by the expression of PRAD1/cyclin D1 or by some other mechanism independent of the amplification of the proto-oncogene.

Adenoma↗

Comparison of gene arrangements of chloroplasts between two centric diatoms, Skeletonema costatum and Odontella sinensis.

We have cloned and sequenced 3.4 kbp, 2.5 kbp, 1.9 kbp, 1.6 kbp and 0.5 kbp segments of a marine centric diatom, Skeletonema costatum, chloroplast DNA. These segments contain 28 genes. The genes which are not encoded on chloroplast genomes of chlorophyll a+b plants are found such as the psaD, ycf33, ycf35 and ycf47 genes. The gene sequences were compared with that of Odontella sinensis. At nucleic acid level, the ycf genes have lower homologies (69-87%) with O. sinensis than the other genes (78-100%), and some differences in the gene arrangement are found between two centric diatoms, O. sinensis and S. costatum.

Chloroplasts↗

Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits.

Animals↗

Molecular cloning of mouse paired-box-containing gene (Pax)-4 from an islet beta cell line and deduced sequence of human Pax-4.

A mouse cDNA encoding paired-box-containing gene (Pax-4) was cloned from a cDNA library of a mouse pancreatic islet beta cell line of MIN6. The predicted open reading frame encodes a protein of 349 amino acids with a calculated molecular weight (MW) of 38-kD. A human Pax-4 cDNA sequence encoding 350 amino acids was deduced from a human cosmid clone. The mouse nucleotide and deduced amino acid sequences exhibit 83.4 and 80.0% identity with those of deduced human Pax-4, respectively. Southern blot analysis suggested that the mouse Pax-4 gene exists as a single copy in the genome. Reverse transcription (RT)-PCR analysis suggested that the mouse Pax-4 gene is expressed in pancreatic islets, cultured islet beta cell lines of MIN6, beta TC, and NIT-1 cells, but not detectable in any of 13 adult mouse organs examined.

Amino Acid Sequence↗

Interaction of mRNAs for angiotensin II type 1 and type 2 receptors to vascular remodeling in spontaneously hypertensive rats.

We administered angiotensin II (Ang II) receptor type 1 (AT1) blockade (losartan, 40 mg x kg-1 x d-1), type II receptor (AT2) blockade (PD123319, 100 mg x kg-1 x d-1), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg x kg-1 x d-1) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT1 receptor, and AT2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT1 and AT2 receptors and ACE in untreated SHR compared with WKY. The AT1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT1 receptor, but not AT2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension.

Angiotensin Receptor Antagonists↗

Interferon-alpha-induced thyroid dysfunction in patients with chronic active hepatitis C: a transient, reversible and self-limited dysfunction.

To survey the prognoses of interferon-alpha (IFNalpha)-induced thyroid dysfunction, a total of 100 patients (49 males and 51 females) with biopsy-proven chronic active hepatitis C were studied. Either during or after IFNalpha therapy, 29 patients (33.7%) revealed suppression/elevation of thyroid stimulating hormone (TSH) or both, transient thyrotoxicosis (TSH less than 0.1 microU/ml) or transient hypothyroidism (TSH 5.0-190.95 microU/ml). However, the thyroid function normalized without supplementation of the thyroid hormone in the follow-up period. In the same period, one of the 14 control patients (7.1%) developed thyroid dysfunction. Thyroid abnormalities developed significantly more in patients with IFNalpha therapy than in those without IFNalpha therapy. The findings suggest that the occult autoimmune disorder becomes overt with IFNalpha treatment in patients with pre-existent autoimmune thyroid disease. IFNalpha-induced thyroid dysfunction is transient, reversible and self-limited. It is not necessary to discontinue IFNalpha therapy when thyroid dysfunction develops.

Adult↗

Laboratory-scale bioremediation of oil-contaminated soil of Kuwait with soil amendment materials.

A huge amount of oil-contaminated soil remains unremediated in the Kuwait desert. The contaminated oil has the potentiality to cause pollution of underground water and to effect the health of people in the neighborhood. In this study, laboratory scale bioremediation experiments were carried out. Hyponex (Hyponex, Inc.) and bark manure were added as basic nutrients for microorganisms, and twelve kinds of materials (baked diatomite, microporous glass, coconut charcoal, an oil-decomposing bacterial mixture (Formula X from Oppenheimer, Inc.), and eight kinds of surfactants) were applied to accelerate the biodegradation of oil hydrocarbons. 15% to 33% of the contaminated oil was decomposed during 43 weeks' incubation. Among the materials tested, coconut charcoal enhanced the biodegradation. On the contrary, the addition of an oil-decomposing bacterial mixture impeded the biodegradation. The effects of the other materials were very slight. The toxicity of the biodegraded compounds was estimated by the Ames test and the tea pollen tube growth test. Both of the hydrophobic (dichloromethane extracts) and hydrophilic (methanol extracts) fractions showed a very slight toxicity in the Ames test. In the tea pollen tube growth test, the hydrophobic fraction was not toxic and enhanced the growth of pollen tubes.

Biodegradation, Environmental↗

Molecular mechanism of angiotensin II type I and type II receptors in cardiac hypertrophy of spontaneously hypertensive rats.

We administered angiotensin (Ang) II receptor type 1 (AT1) blockade (losartan; 10 or 40 mg/kg per day), type II receptor (AT2) blockades (PD123319; 100 mg/kg per day), or angiotensin-converting enzyme (ACE) inhibitor (enalapril; 30 mg/kg per day) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. At the end of the treatment, high doses of losartan and enalapril significantly reduced the arterial systolic blood pressure compared with the untreated SHR to the level of WKY rats. But low doses of losartan and PD123319 were without effect. High doses of losartan and enalapril also significantly reduced both the left ventricular (LV) weight and the ratio of LV to body weight compared with the untreated SHR, which were still larger than that of WKY rats. However, the collagen concentration of SHR treated with high doses of losartan or enalapril was completely reduced to the level of WKY rats. Using reverse transcription polymerase chain reaction, we examined the mRNA expression for ACE, AT1, and AT2 in experimental animals. The enhanced AT1 mRNA expression was significantly decreased in the SHR treated with a high dose of losartan or PD123319 compared with the untreated SHR. The level of ACE mRNA was also decreased in the SHR treated with a high dose of losartan or enalapril. The level of AT2 mRNA was not significantly different between the Wistar-Kyoto rats and the SHR; however, this expression was decreased significantly after the treatment with a high dose of losartan or PD123319. These results indicate that AT1 receptor and ACE, but not AT2 receptor, play a crucial role in the remodeling of matrix tissue but a smaller role in the development of the hypertrophy of LV myocyte in SHR and that the LV/body weight changes do not fully account for the complete suppression of hypertension.

Angiotensin Receptor Antagonists↗