Biomedical subjects

S Toda

Publications and source records attributed to S Toda.

At least 19 recordsLinked to original sources

PubMed2000

Reciprocal expression of infant- and adult-preferring transcripts of CDCrel-1 septin gene in the rat neocortex.

We report here the isolation and characterization of cDNA clones for a novel isoform of CDCrel-1 septin, termed CDCrel-1A, with a different 5' end sequence from the transcripts encoding the known CDCrel-1 (designated as CDCrel-1F) in the developing rat neocortex. Alternative polyadenylation site selections resulted in various transcripts for CDCrel-1A including the fusion forms with another gene, platelet glycoprotein Ibbeta (GPIbbeta). Expression of the distinct transcripts encoding CDCrel-1A and CDCrel-1F increased and decreased, respectively, from the infant to adult period. Therefore CDCrel-1A might be a major form of the CDCrel-1 septin in the adult neocortex of mammals.

Amino Acid Sequence↗

PubMed2000

An air-liquid interface promotes the differentiation of gastric surface mucous cells (GSM06) in culture.

The gastric surface epithelium is situated at an air-liquid interface because the luminal surface of the alimentary tract is in continuity with the air phase. However, the effects of this microenvironment on the gastric epithelium remain unclear. The aim of this study was to clarify the effects of an air-liquid interface on gastric epithelial cell biology. Gastric surface mucous cells (GSM06) were cultured at an air-liquid interface. Cultured cells were examined by histology, histochemistry, and transmission electron microscopy. When the cells were cultured at an air-liquid interface, the surface cells on the collagen gel became tall columnar and secreted periodic acid-Shiff-positive substances at the apical surface. These cells indicated many mucous granules in the apical cytoplasm and organized the basal lamina at the contact side with the gel. In contrast, under immersed condition, the surface cells showed immature features. This is the first report of an air-liquid interface promoting the differentiation of gastric surface mucous cells in a reconstruction culture of the gastric surface epithelial layer, suggesting that an air-liquid interface may function as a crucial luminal factor to maintain the homeostasis of gastric mucosa.

Air↗

PubMed2000

Heightened odds of large earthquakes near istanbul: An interaction-based probability calculation

We calculate the probability of strong shaking in Istanbul, an urban center of 10 million people, from the description of earthquakes on the North Anatolian fault system in the Marmara Sea during the past 500 years and test the resulting catalog against the frequency of damage in Istanbul during the preceding millennium. Departing from current practice, we include the time-dependent effect of stress transferred by the 1999 moment magnitude M = 7.4 Izmit earthquake to faults nearer to Istanbul. We find a 62 +/- 15% probability (one standard deviation) of strong shaking during the next 30 years and 32 +/- 12% during the next decade.

Journal Article↗

PubMed2000

Air exposure promotes fibroblast growth with increased expression of mitogen-activated protein kinase cascade.

Subepithelial tissue cell types in vivo are separated from air by the surface-covering epithelial layer of various organs, e.g., the skin, cornea, and respiratory and upper alimentary tracts. The epithelial defect caused by inflammatory, traumatic or surgical injury would be expected to expose the subepithelial tissue-localized fibroblasts to influx air. However, it is unclear what effects air stimulation elicits in fibroblast growth, which is critical for wound healing. To address this question, we examined the proliferation of 3T3 fibroblasts with bromodeoxyuridine (BrdU) uptake, using fibroblast-embedded collagen gel culture with or without air exposure. The BrdU intake of air-exposed fibroblasts was about 6 times that of air-nonexposed cells. To further characterize this fibroblast growth, we examined the expression of mitogen-activated protein kinase (MAPK) cascade, which plays a key role in the growth-signaling pathway of various cell types. Immunohistochemistry and Western blotting showed that air exposure increased MAPK cascade expression of the cells more strongly than air nonexposure. The data indicate that air exposure promotes MAPK cascade-associated fibroblast growth, suggesting in turn that in wound repair air stimulation itself may be involved in the basic mechanisms of subepithelial fibroblast proliferation and that it may be related to the pathogenesis of excessive fibroplasia through fibroblast overgrowth.

3T3 Cells↗

PubMed2000

Inhibitory effects of astragali radix, crude drug in Oriental medicines on lipid peroxidation and protein oxidative modification of mouse brain homogenate by copper.

Astragali Radix, the root of Astragalus membranaceus Bunge, is a crude drug used widely in Oriental medicines. It is a major component of Ougi-Keishi-gomotsu-to, a traditional herbal medicine, used for neurop patients with abnormal sensations and neuropathic pain of the legs. It was shown to have inhibitory effects on lipid peroxidation and protein oxidative modification by copper. The effects were similar to and stronger than those of mannitol and superoxide dismutase as free radical scavengers. These results demonstrated that Astragali Radix has inhibitory effects on oxidative stress induced by metal.

Animals↗

PubMed2000

8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine.

From a series of preclinical studies and animal experiments, we have been able to demonstrate that DNA vaccines are a promising tool in strategies for protecting hosts from a variety of infectious diseases. Since the promoter activity of the human cytomegalovirus immediate-early promoter/ enhancer (CMV promoter) is known to be responsive to an elevation in the level of intracellular cAMP, we hypothesized that use of cAMP analogue (8-Bromo adenosine 3'5'-cyclic monophosphate, 8 Br-cAMP) would increase the level of transgene expression supported by the CMV, and enhance the ability of DNA vaccines to evoke an immune response against the transgene product in vivo. To evaluate this hypothesis, immune responses against HIV-1 envelope protein, gp160, an immunogenic HIV-1 component expressed under the control of the CMV promoter, were evaluated in BALB/c mice with or without stimulation by 8 Br-cAMP. DNA vaccine with 8 Br-cAMP was intramuscularly (i.m.) or intranasally (i.n.) administered to BALB/c mice twice on days 0 and 14. Regardless of which route was used, the combination increased the serum IgG antibody (Ab) titer, HIV-1-specific cytotoxic T lymphocyte (CTL) activity and the delayed-type hypersensitivity (DTH) response, compared with the effect of using the vaccine alone. When administered via the i.n. route, the combination also remarkably increased the titer of secretory IgA (sIgA). Moreover, it induced increased production of interferon-gamma with reduction in IL-4 synthesis, and decreased the ratio of serum IgG1/IgG2a. However, these enhancements were not observed when 8 Br-cAMP was coadministered with peptide vaccine or protein antigen. These data suggest that 8 Br-cAMP is able to enhance both humoral and cellular immune responses induced by the DNA vaccine. The induction of T helper type 1 (Th1) immunity against HIV-1 was also enhanced by coadministration of 8 Br-cAMP. A CAT assay study demonstrated that the adjuvant effect of 8 Br-cAMP may be due to the activation of the CMV promoter in the DNA vaccine. The virus challenge experiment in a mouse influenza model also proved our hypothesis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Growth factor-expressing mast cells accumulate at the thyroid tissue-regenerative site of subacute thyroiditis.

The localization and biological roles of the multifunctional cell type mast cells remain unclear in subacute thyroiditis that is characterized by both epithelioid granuloma formation and thyroid tissue repair. We examined their immunolocalization with tryptase of a mast cell marker, using the biopsy specimens from 12 cases. In the epithelioid granuloma, no mast cells were detected in any of the cases, although a small number of them (4.6 +/- 2.4) were seen at the fibrous stroma around the granuloma in all cases. By contrast, in all cases, increased mast cells (28 +/- 7.2) localized at the thyroid tissue-regenerative site where both thyroid folliculogenesis and angiogenesis take place. To elucidate possible roles of mast cells in the disease, we also examined their immunoexpressions of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF), which affect thyroid folliculogenesis and angiogenesis. In all 12 cases, mast cells displayed all of these growth factors in a manner not specific to the infiltrating site. The data suggest that growth factor-expressing mast cells may play crucial roles in the thyroid tissue repair of subacute thyroiditis, modulating thyroid folliculogenesis and angiogenesis; and that the multifunctionality of the cells may be partly dependent on their expressions of various growth factors.

Acute Disease↗

PubMed2000

Establishment of a ciliated epithelial cell line from human Fallopian tube.

Human tubal epithelial cells in primary culture were transfected with simian virus 40 (SV40) large T antigen plasmid, and an immortalized ciliated cell line, named as NT/T-S, was established without crisis. Transmission electron microscopy proved that NT/T-S cells had cilia, microvilli, junctional complexes, rough endoplasmic reticula, free ribosomes and microtubules. NT/T-S cells were evaluated preliminarily on the basis of co-culture study using surplus embryos at the 4- to 8-cell stage in our IVF and embryo transfer programme. All of the 133 embryos had >/=10% fragments (based on the surface area) and were unworthy of cryopreservation. Up to 57% (16/28) of the embryos with 10-30% fragments reached the blastocyst stage by co-culture. In contrast, blastocyst formation was observed in <10% of the control embryos, some of which were co-cultured with NFL/T cells (the immortalized human fetal liver epithelial cells) (1/16), and the others were incubated with the co-culture medium alone (1/18). Various cytokines/growth factors such as leukaemia inhibitory factor (LIF), interleukin (IL)-6, IL-8 and basic fibroblast growth factor were secreted by NT/T-S cells as well as by the tubal epithelial cells in primary culture. The establishment of a ciliated cell line will provide a valuable resource for the further studies of the Fallopian tube in the early events of pregnancy.

Blastocyst↗

PubMed2000

Two inbred strains of rats, Fischer 344 and Lewis, showed differential behavior and brain expression of corticosterone receptor mRNA induced by methamphetamine.

Recently, a role of the hypothalamo-pituitary-adrenocortical (HPA) axis in facilitating the behavioral and neurochemical effects of psychostimulants has been proposed. Two inbred strains of rats, Fischer 344/N (F344) and Lewis/N (LEW), have markedly different HPA axes as well as behavioral responses to psychostimulants: F344 rats show hyperresponsive HPA axis and no significant sensitization to cocaine, whereas LEW rats display blunted response in HPA axis and develop cocaine-induced locomotor sensitization. Corticosterone exerts its biological effects via intracellular receptors, termed type I (mineralocorticoid receptor: MR) and type II (glucocorticoid receptor: GR). The present study examines the development of stereotypy sensitization and the brain expression of mRNAs for MR, GR, and heat shock protein 90 (HSP90) in methamphetamine (MAP)-treated F344 and LEW rats. Animals received i.p. injections with chronic saline (SAL: once daily for 21 days), chronic saline and acute MAP (AM: saline for 20 days and 4 mg/kg MAP on the 21st day), or chronic MAP (CM: 4 mg/kg MAP for 21 days) and were sacrificed three hours after the last injections. Striatum, hippocampus, and cerebellum were quickly dissected on ice and total RNA was isolated for northern analyses. LEW rats developed stereotypy sensitization significantly earlier than F344 rats. AM significantly decreased GR and MR mRNA expression in hippocampus of LEW, compared to SAL. CM significantly increased GR and MR mRNA expression in striatum of F344 compared to SAL and AM, while it decreased GR mRNA in striatum of LEW and MR mRNA in hippocampus, compared to SAL. AM significantly increased HSP90 mRNA in all brain regions examined, without the hippocampus in LEW. CM significantly increased the expression of HSP90 mRNA in the striatum and cerebellum of F344, but significantly decreased in the striatum and hippocampus of LEW. These contrasting differences between F344 and LEW, in their susceptibility to stereotypy sensitization and striatal expression of GR mRNA by chronic MAP, suggest that some striatal genes, whose transcription is regulated by GR, play a crucial role in the development of MAP-induced behavioral sensitization.

Animals↗

PubMed2000

Image analysis of olfactory responses in the procerebrum of the terrestrial slug Limax marginatus.

Neural oscillations have been found to occur in the olfactory centers of some vertebrates and invertebrates, including the procerebrum of the terrestrial slug Limax marginatus. Using optical recording with the potential-sensitive dye di-4-ANEPPS, we analyzed the spatiotemporal pattern of procerebral neural activities in response to odorants applied to an in vitro brain-superior tentacle preparation. The odor of rat chow, on which the slugs were normally fed, increased the frequency of the oscillation. Garlic odor, which induced aversive behavior in the slug, caused a transient increase in oscillation frequency during stimulation, followed by a second increase in oscillation frequency when the stimulus was terminated. Wave propagation from the distal to the proximal region of the procerebrum was accelerated in parallel with modulation of the frequency. The cycle-by-cycle average of the optical signals showed that a large area of the cerebral ganglia, including the procerebrum, was depolarized during the initial increase in frequency. During the second increase, however, the net depolarization was most prominent in the terminal mass of the procerebrum. These results suggest that the level of depolarization generated by interactions among the neurites projecting to the terminal mass, such as the neurites of the nonbursting neurons, may control neural oscillations in the procerebrum.

Animals↗

PubMed2000

[Therapeutic effect and clinical findings in patients with MPO-ANCA associated vasculitis syndrome].

We investigated to clarify the clinical findings, course and therapeutic effect in the patients with MPO (myeloperoxidase)-ANCA (anti-neutrophil cytoplasmic antibody) associated vasculitis syndrome. We analyzed clinical findings and data of 19 cases of MPO-ANCA associated vasculitis. These patients were diagnosed with clinical symptoms (fever, arthralgia, body weight loss, etc.), laboratory data (high titer of CRP, leukocytosis, thrombocytosis, and high titer of MPO-ANCA) and pathologic findings of necrotizing vasculitis. They were 14 male and 5 female aged 18 to 84 years (mean 65 years) and were treated with prednisolone and immunosuppressive agents, and additional therapy included pulse therapy and plasma exchange. Seven cases were dead within 3 months. Post-mortum examination showed that these cases died of pneumonitis, cerebral events and gastric bleeding. There was no mortal case induced by over-immunosuppression. In survival cases, the MPO-ANCA levels decreased rapidly after these therapies and these antibodies were maintained low levels (360 to 25 EU/l). Comparison of fatal cases and survival cases, there were difference in the initial dose of prednisolone (27 mg/day vs. 56 mg/day), the ratio of double filtration plasmapheresis (14% vs. 42%), and the ratio of immunosuppressive therapy (14% vs. 83%). The measurement of MPO-ANCA is useful makers of the diagnosis and effectiveness of the therapy in patients with MPO-ANCA associated vasculitis. We recommend the aggressive therapy, including prednisolone, immunosuppressive agents and plasma exchange for MPO-ANCA associated vasculitis. We believe that the aggressive therapy improve the survival rate of the patients with MPO-ANCA associated vasculitis.

Adolescent↗

PubMed2000

[Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency].

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.

Adult↗

PubMed1999

Inhibitory effects of Astragali Radix, a crude drug in Oriental medicines, on lipid peroxidation and protein oxidative modification by copper.

Effects of Astragali Radix, the root of Astragalus membrauaceus Bunge, were investigated on oxidative stress such as lipid peroxidation and protein oxidative modification by copper. The results showed that these effects are similar to those of mannitol and superoxide dismutase as a free radical scavenger. It was demonstrated that Astragali Radix have inhibitory effects on oxidative stress induced by copper.

Copper↗

PubMed1999

Effects of stromal fibroblasts and fat cells and an environmental factor air exposure on invasion of laryngeal carcinoma (HEp-2) cells in a collagen gel invasion assay system.

OBJECTIVE: To clarify the invasion mechanism of laryngeal carcinoma (HEp-2) cells. DESIGN: Human HEp-2 cells were cultured on a collagen gel containing fibroblasts and/or fat cells. The HEp-2 cells were also treated with air exposure as the local environment of the laryngeal epithelial mucosa. A collagen gel invasion assay was conducted under these culture conditions. RESULTS: No invasion of HEp-2 cells was found in the stromal cell-free collagen gel, but a slight invasion was observed in the fibroblast-embedded gel. A deeper invasion of HEp-2 cells occurred in the fibroblast- and fat cell-coembedded gel and in the fibroblast-embedded gel with air exposure. The most extensive invasion of HEp-2 cells was observed under the fibroblast- and fat cell-coembedded gel in combination with air exposure. CONCLUSIONS: Fat cells and air exposure clearly increase the invasive effect of fibroblasts in squamous cell carcinoma of the larynx. The combined effect of these 3 factors (ie, fat cells, fibroblasts, and air exposure) plays a very important role in the invasive growth of the carcinoma cells. This observation suggests that both tumor cell-stromal cell interaction and tumor cell-local environmental factor interaction should be taken into account in an investigation of the invasive and proliferative mechanisms of laryngeal carcinoma.

Adipose Tissue↗

PubMed1999

Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture.

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) in the inflammatory process, their immunoexpression was examined in biopsy specimens of ten cases. At the granulomatous stage, all cases expressed VEGF, bFGF, PDGF, and TGF-beta1 in monocytes/macrophages infiltrating into follicle lumina, and in both epithelioid histiocytes and multinucleated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-beta1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expressed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no cases displayed PDGF and TGF-beta1, respectively. Ten, seven and six cases expressed PDGF in fibroblasts, endothelial cells, and monocytes, respectively. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta1 and EGF. To estimate the roles of these growth factors in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes and endothelial cells, respectively. Cell proliferation was also studied by bromodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-beta1 drastically inhibited it, but the others had no effect. VEGF showed the greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and endothelial cells, respectively. The data suggest firstly, that at the granulomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrophages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta1 produced by the stromal cell types tested mediate the reaction; secondly, that at the regenerative stage, EGF serves follicle regeneration through its mitogenic effect on thyrocytes, although some cofactors with EGF are involved in folliculogenesis and the decreased expression of TGF-beta1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied.

Cell Culture Techniques↗

PubMed1999

Inhibitory effects of isoflavones on lipid peroxidation by reactive oxygen species.

Possible inhibitory effects were investigated for four isoflavones, biochanin A, daidzein, formononetin and genistein on lipid peroxidation by reactive oxygen species. Biochanin A, formononetin and genistein inhibited lecithin peroxidation which was induced by hydroxy radical generation, by interaction of haemoglobin and hydrogen peroxide. Daidzein and formononetin inhibited lecithin peroxidation which was induced by superoxide anion generation by xanthine-xanthine oxidase. These results demonstrated that the differences in antioxidant activities of isoflavones are dependent on the relation between their chemical structures and reactive oxygen species.

Anticarcinogenic Agents↗

PubMed1999

Inhibitory effects of Ougi-keishi-gomotsu-to, a traditional herbal medicine, on lipid peroxidation and protein oxidative modification of mouse brain homogenate induced by copper.

Ougi-Keishi-gomotsu-to a traditional herbal medicine, is used clinically for patients with abnormal sensations and pain in the legs in neuropathy. It was shown to have inhibitory effects on lipid peroxidation and protein oxidative modification of brain homogenate induced by copper. Its effect was stronger than those of mannitol and alpha-tocopherol as free radical scavenger and antioxidant. These results demonstrated that Ougi-kelshi-gomotsu-to has antioxidative effects on neuron injury derived from oxidative stress induced by metal.

Animals↗

PubMed1999

Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency.

The prenatal diagnosis of peroxisomal D-3-hydroxyacyl-coenzyme A (CoA) dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP) deficiency was performed by peroxisomal beta-oxidation assay, indirect immunofluorescence staining, immunoblot analysis, and gene analysis of cultured amniocytes obtained from a fetus at 16 weeks' gestational age. beta-Oxidation activity, measured by [1-14C] lignoceric acid oxidation, was markedly decreased compared with the controls. Large peroxisomes were readily identified by immunofluorescence staining with anti-human catalase, as was found in the reported patients. Immunoreactive D-BP material was absent on immunoblot analysis and immunofluorescence staining with anti-human D-BP. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of the same 237-bp deletion in the cDNA as that detected in a sibling (the proband). The autopsied fetus showed the characteristic facial appearance and D-BP was deficient on immunoblot and immunohistopathological studies of the fetal tissues. No neuronal migration disorder was identified. This seems to be the first prenatal diagnosis of D-BP deficiency.

17-Hydroxysteroid Dehydrogenases↗