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Biomedical subjects

S Tanaka

Publications and source records attributed to S Tanaka.

At least 217 records · Page 12Linked to original sources

Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors.

Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.

Animals↗

Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases.

Tumor angiogenesis progresses by a dynamic balance between tumor vascular regression and growth. Angiopoietin (Ang)-2 (the natural antagonist for the angiogenic Tie-2 receptor) and vascular endothelial growth factor (VEGF) are thought to be critical regulators in this process; therefore, these may play a critical role in cancer aggressiveness. The aim of this study was to clarify the clinical and biological significance of the expression of Ang-2 in human gastric cancers and to investigate the relationship between Ang-2 together with VEGF and the induction of proteases such as matrix metalloproteinases (MMPs) in the process of tumor development. Eighty-five individuals with gastric cancer, who had undergone surgery without preoperative treatment, were studied. A stable transfectant of the human MKN-7 gastric cancer cell lines with an Ang-2 expression vector was used for the experimental study. First, we examined the relationship between the mRNA expression of Angs by Northern blot analysis and clinicopathological features. High Ang-2-expression cases showed more frequent vascular involvement and more advanced stages of disease compared with low Ang-2-expression cases (P < 0.05). With regard to prognosis, the survival time for patients in the high-Ang-2 mRNA group was significantly shorter (P < 0.05). When we examined the localization of Ang-2 in human gastric cancers, immunohistochemical analysis revealed that this protein was expressed predominantly in cancer tissues when compared with normal tissues. Interestingly it was expressed not only in endothelia cells (ECs) but also in cancer cells. Second, Ang-2-transfected cells were implanted in vivo into the gastric walls of nude mice. Ang-2-transfectant mice developed highly metastatic tumors with hypervascularity as compared with MKN-7 or control vector-transfectant tumors. There was a significant correlation between Ang-2 mRNA expression and lower grade of vessel maturation. Third, on the basis of the in vivo data, we focused on production of proteases such as MMPs to investigate possible mechanisms in these processes. MMP-1, MMP-9, and urokinase-type plasminogen activator in ECs were strongly up-regulated by Ang-2 in the presence of VEGF in vitro. These data suggest that production of Ang-2 is implicated in tumor development in human gastric cancers. Its production may contribute to tumor angiogenesis by induction of proteases in ECs, which may be enhanced in the presence of VEGF.

Angiopoietin-2↗

PAL31, a nuclear protein required for progression to the S phase.

PAL31 is a nuclear protein expressed by various cell types. In the present study, the expression and function of PAL31 were examined in the cytokine-regulated growth of T and B cell lines. Treatment of the cells with mitogens [ovine PRL, recombinant rat placental lactogen-I (PL-I) and human IL-3] caused a dose-dependent increase in the expression of PAL31 mRNA in the PRL-dependent cell line Nb2, and IL-3 dependent cell line BaF3. A time-course study on synchronized Nb2 cells revealed that the expression of PAL31 is specific to the late G1 and S phases. Immunocytological studies revealed that PAL31 accumulates in the nuclei at the S phase. Furthermore, the antisense oligonucleotide for PAL31 severely inhibited the proliferation of Nb2 cells by inhibiting cells progressing to the S phase. Thus, PAL31 is a nuclear protein associated with cell cycle progression.

Animals↗

Acute effects of ovariectomy on wound healing of alveolar bone after maxillary molar extraction in aged rats.

Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption.

Acute Disease↗

Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model.

Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.

Animals↗

Determination of bufalin-like immunoreactivity in serum of humans and rats by time-resolved fluoroimmunoassay for using a monoclonal antibody.

The existence of a mammalian natriuretic substance or endogenous digitalis-like factor, which inhibits Na+,K+-ATPase and thereby regulates body fluid volume, has been speculated for a long time but has yet to be defined. We established in the present study a simple and highly sensitive procedure to measure bufalin, a constituent of toad venom preparation and a specific inhibitor of Na+,K+-ATPase by time-resolved fluoroimmunoassay (TR-FIA) and using a monoclonal antibody. The antibody was specific to bufalin and resembled bufadienolides but showed no cross-reactivity with digitoxin and ouabain. A bufalin-like immunoreactivity was detectable in serum of humans and rats by the proposed TR-FIA. The levels of bufalin-like immunoreactivity in serum of healthy volunteers were significantly correlated with their systolic blood pressure. Moreover, bufalin-like immunoreactivity in serum of Dahl-S rats increased in parallel with a period of high-salt diet. These results suggest that increased bufalin-like immunoreactivity may be associated with certain types of hypertension.

Animals↗

High-pressure NMR study of cis-1,n-disubstituted[n]paracyclophanes. Effect of increased pressure on the hindered internal rotation.

The effect of hydrostatic pressure on the rate of internal rotation of title compounds has been examined by the DNMR method. Quartz pressure-resisting NMR cells were used to realize the high-pressure experiments up to 390 (line shape measurements) and 450 MPa (chemical shift measurements). Application of hydrostatic pressure was found to accelerate the rotation of the benzene ring, while pressure-induced low-frequency chemical shifts of bridge methylene protons indicated that there is a considerable shrinkage of the methylene bridge structure upon pressurization.

Journal Article↗

Effects of suppressed oviposition activity and flight muscle histolysis on food consumption and ovarian development in a wing-dimorphic cricket: an explanation for sporadic conclusions related to physiological trade-offs.

The effects of deprivation of oviposition substrate on food consumption and egg production were compared between the long-winged (LW) and the short-winged (SW) morph of a cricket, Modicogryllus confirmatus, to determine how suppressed oviposition activity would influence these traits in each wing morph. Food consumption was greatly suppressed in females deprived of oviposition substrate (-OS) compared to those given access to it (+OS) during the 2-week feeding trial in the SW morph but not in the LW morph. Some LW females shed their hindwings and histolyzed the flight muscles. Such de-alated LW (DLW) morphs tended to consume more food than intact LW (ILW) morphs. In all morphs, ovarian weight was heavier under -OS conditions than under +OS conditions during the second week of adulthood, although the differences were greater in SW morphs than in ILW morphs. In DLW morphs in which flight muscle histolysis was induced by artificial de-alation at adult emergence, the temporal changes in ovarian weight were similar to those of SW morphs.In SW morphs, food consumption was also significantly reduced when ovipositing females were deprived of oviposition substrate for 2 days compared to those allowed to oviposit continuously, but food consumption was not reduced in ILW or DLW morphs. SW females from which one ovary was extirpated at adult emergence, SW (-o), also showed a significant difference in food consumption when treated as above, indicating that food consumption was not determined simply by the number of ovarian eggs. The crop content was positively correlated to food consumption and smaller under -OS conditions than under +OS conditions. The 2-day deprivation of oviposition substrate caused no significant difference in the total number of deposited and ovarian eggs in any group, but the ovarian mass of developing oocytes tended to be smaller under -OS than under +OS conditions, particularly in SW morphs.These results indicate the possibility that some inconsistent results and conclusions discussed in recent studies, concerning the physiological trade-offs between flight capability and reproduction, were caused by the suppressed oviposition activity and failure to recognize the occurrence of flight muscle growth and histolysis in the test crickets.

Journal Article↗

Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial.

HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. DESIGN: A prospective randomized trial. SETTING: A university hospital department of surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.

Acute-Phase Proteins↗

Prevalence and risk factors of tendinitis and related disorders of the distal upper extremity among U.S. workers: comparison to carpal tunnel syndrome.

BACKGROUND: National estimates of tendinitis and related disorders of the distal upper extremity among U.S. workers have not been available with the exception of carpal tunnel syndrome. METHODS: The Occupational Health Supplement Data of the 1988 National Health Interview Survey were analyzed for tendinitis and related disorders of the hand/wrist and elbow (distal upper extremity) using the Survey Data Analysis (SUDAAN) software. RESULTS: Among the 30,074 respondents (statistically weighted population of 127 million) who had worked anytime during the previous 12 months, 0.46% (95% CI: 0.36, 0.56) reported that they experienced a "prolonged" hand discomfort which was called tendinitis, synovitis, tenosynovitis, deQuervain's disease, epicondylitis, ganglion cyst, or trigger finger, by a medical person. This corresponds to 588,000 persons (95% CI: 457,000; 712,000) reporting one of these disorders, 28% (or 164,000) of which were thought to be work-related by the medical person. Among various risk factors examined by multiple logistic regression analysis, bending/twisting of the hands/wrists at work and female gender were significantly associated with reporting of these disorders. CONCLUSIONS: By combining these cases with the previously reported cases of work-related carpal tunnel syndrome, we estimate that there were approximately 520,000 cases of work-related musculoskeletal disorders of the distal upper extremity among US workers in 1988.

Adolescent↗

Endocrine mechanisms controlling body-color polymorphism in locusts.

The present article reviews recent published and unpublished findings on the hormonal mechanisms for the control of body-color polymorphism in locusts. Emphasis is placed on the dark color-inducing factors and their role in the induction of various types of body coloration observed under different environmental conditions. Implantation of corpora cardiaca (CC) taken from normal nymphs of Locusta migratoria induced dark color in nymphs of an albino strain. Using the albino strain for the bioassay, a neuropeptide, [His7]-corazonin, was identified as a dark color-inducing factor for L. migratoria and Schistocerca gregaria. In the former, depending upon the dose and timing of the injection, this peptide and juvenile hormone developed various body colors looking like those found in nature. The body coloration characteristic of gregarious forms was also induced in isolated albino nymphs and field-collected solitary nymphs. In S. gregaria, on the other hand, the peptide induced black patterns, but the orange or yellow background color observed in gregarious forms was not induced when the peptide was injected into solitary individuals. [His7]-corazonin also induced darkening in other grasshoppers and locusts, but not in katydids. Albino L. migratoria developed dark color when implanted with brains or CC taken from other insects belonging to 10 major insect orders, but not with those from Coleoptera. [His7]-corazonin or a similar compound is widespread among insects and plays a pivotal role in controlling body color in some species and presumably other physiological roles in other species. Arch.

Animals↗

Mass spectrometric evidence for the deficiency in the dark-color-inducing hormone,.

A factor present in the brain and corpus cardiacum responsible for the induction of dark colour in Locusta migratoria was recently isolated and identified from the corpora cardiaca of normally pigmented locusts. The purification of this factor, designated as [His7]-corazonin was monitored using an albino mutant from a laboratory colony of an Okinawa (Japan) strain. In this study, we provide unequivocal mass spectrometric evidence that the brain and the corpora cardiaca of this albino Locusta mutant are deficient in [His7]-corazonin. Previously, [His7]-corazonin was shown to be responsible for the induction of dark body colour patterns as observed in crowded locusts. Using nanoflow-liquid chromatography-mass spectrometry, we demonstrated that this dark colour-inducing hormone is, however, present in the corpora cardiaca of solitary locusts (Schistocerca gregaria). Arch.

Animals↗

Identification of reaction products of methamphetamine and hydrogen peroxide in hair dye and decolorant treatments by high-performance liquid chromatography/mass spectrometry.

The effect of hydrogen peroxide, a main component of hair dye and decolorant treatments, on methamphetamine (MA) was studied. Two analytical methods, thin-layer chromatography (TLC) and high-performance liquid chromatography/mass spectrometry (LC/MS), were used for the separation and identification of MA derivatives. Mixtures of MA solutions and hydrogen peroxide that had been incubated at 39 degrees C for 24 h were shown to contain para-hydroxy MA by TLC and para-, meta- and ortho-hydroxy MAs by LC/MS. In addition, MA N-oxide and N-hydroxy MA were found in MA/hydrogen peroxide mixtures immediately after mixing. Therefore, we concluded that MA changed to MA N-oxide and N-hydroxy MA before changing to para-, meta- and ortho-hydroxy MAs.

Chromatography, High Pressure Liquid↗

DNA methylation variation in cloned mice.

Mammalian cloning has been accomplished in several mammalian species by nuclear transfer. However, the production rate of cloned animals is quite low, and many cloned offspring die or show abnormal symptoms. A possible cause of the low success rate of cloning and abnormal symptoms in many cloned animals is the incomplete reestablishment of DNA methylation after nuclear transfer. We first analyzed tissue-specific methylation patterns in the placenta, skin, and kidney of normal B6D2F1 mice. There were seven spots/CpG islands (0.5% of the total CpG islands detected) methylated differently in the three different tissues examined. In the placenta and skin of two cloned fetuses, a total of four CpG islands were aberrantly methylated or unmethylated. Interestingly, three of these four loci corresponded to the tissue-specific loci in the normal control fetuses. The extent of aberrant methylation of genomic DNA varied between the cloned animals. In cloned animals, aberrant methylation occurred mainly at tissue-specific methylated loci. Individual cloned animals have different methylation aberrations. In other words, cloned animals are by no means perfect copies of the original animals as far as the methylation status of genomic DNA is concerned.

Animals↗

Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.

Animals↗