[Infection of mycoplasma].
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AIDS-Associated Nephropathy↗
Biomedical subjects
S Sakuma
Publications and source records attributed to S Sakuma.
Receptor protein tyrosine kinase DDR is up-regulated by p53 protein.
We have previously reported on radiation-induction of ptk-3 in rat astrocyte culture [Sakuma et al. (1995) Radiat. Res. 143, 1-7]. Ptk-3 was considered to be a rat version of human DDR (discoidin domain receptor). We cloned and analyzed genomic DNA of the DDR and its promoter region. We discovered that the promoter region contained a consensus sequence of the p53 tumor suppressor binding site. Adenovirus-mediated p53 transfection induced a high level of DDR mRNA in SAOS2 human osteosarcoma cells. These results indicate that DDR is up-regulated by the p53 protein.
Blotting, Northern↗
Clonality and stability of the p53 gene in human astrocytic tumor cells: quantitative analysis of p53 gene mutations by yeast functional assay.
Mutation of the p53 gene is found in about one third of astrocytic brain tumors, and expansion of tumor cell clones containing mutant p53 has been implicated in astrocytic tumor progression. However, admixture of normal cells in astrocytic tumor specimens limits the power of traditional studies of tumor cell clonality. To address this problem we have employed a yeast p53 functional assay that scores the content of mutant p53 alleles in tumors and cell lines quantitatively. We have analyzed 17 cases where matching tumor material and derived cell lines were available. The yeast assay gave > 20% red (i.e., mutant p53-containing) yeast colonies in 7 out of 17 cases. One case had no mutations in the primary tumor but gave 76% red colonies in a recurrence, clearly demonstrating tumor overgrowth by a mutant clone. During early passages of cultured tumor cells, mutant p53 content increased rapidly with passage due to outgrowth of mutant clones from a heterogeneous starting population. In addition, de novo p53 mutations appeared during culture in 2 cases. This indicates that there is stronger selective pressure for mutation during the establishment of cell lines in vitro than during tumor growth in vivo. Our results demonstrate the utility of the p53 functional assay for studies of clonality and support the hypothesis of clonal progression of brain tumors in vivo.
Astrocytoma↗
15-Hydroperoxyeicosapentaenoic acid inhibits arachidonic acid metabolism in rabbit platelets more potently than eicosapentaenoic acid.
The effect of 15-hydroperoxy-5,8,11,13,15-eicosapentaenoic acid (15-HPEPE), a hydroperoxy adduct of eicosapentaenoic acid (EPA), on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid in washed rabbit platelets was examined. 15-HPEPE inhibited 12-HETE, TXB2 and HHT formation at concentrations ranging from 2 to 8 microM. The inhibitory effect of 15-HPEPE was dose-dependent (12-HETE, 16.0-82.9% inhibition; TXB2, 16.7-57.2% inhibition; HHT, 4.6-52.0% inhibition). EPA inhibited the production of these three metabolites, but the inhibitory effect was kept low (20-100 microM: 12-HETE, 8.3-31.1% inhibition; TXB2, 18.9-49.5% inhibition; HHT, 12.5-41.7% inhibition) as compared with 15-HPEPE. Experiments utilizing 15-hydroxy-5,8,11,13,15-eicosapentaenoic acid and hydroxyl radical scavengers (dimethyl sulfoxide and mannitol) revealed that 15-HPEPE exerted its effect in the form of the hydroperoxy adduct. These results suggest that 15-HPEPE has the potential to modulate the activities of the cyclo-oxygenase and 12-lipoxygenase in platelets. This may also be one convincing mechanism for the anti-thrombotic and anti-atherosclerotic actions of EPA.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Impairment of phagocytic cell respiratory burst by UVA in the presence of fluoroquinolones: an oxygen-dependent phototoxic damage to cell surface microvilli.
Fluoroquinolones are widely used clinically as broad-spectrum antimicrobial agents. One of their side effects is UVA-dependent photosensitivity, observed after the skin is exposed to sunlight. We have investigated five fluoroquinolones and have found that their phototoxicity is oxygen dependent. Human phagocytic leucocytes were stimulated with serum opsonized zymosan to produce superoxide radical (O2-) (respiratory burst) in the presence of a sensitive O2(-)-specific cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol (1,2-alpha) pyrazin-one hydrochloride (MCLA), as chemiluminescence reagent with which O2- can react to induce photon emission. The photon count was used as a measure of respiratory burst activity. When leucocytes were irradiated with UVA for 10 min in the presence of 3 micrograms ml-1 lomefloxacin, ciprofloxacin or norfloxacin, a marked decrease in respiratory burst activity was observed; in this respect, ofloxacin and tosufloxacin were weak. Scanning electron microscopy revealed that the cell surface microvilli were destroyed. The phototoxicity of fluoroquinolones could be abolished if oxygen in the tests was replaced by nitrogen or if the aminothiol DL-cysteine (1.5 mg ml-1) was added prior to irradiation. It is suggested that an oxygen species derived from UVA-excited drug molecules and oxygen mediates the phototoxicity of these fluoroquinolones.
Anti-Infective Agents↗
Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of prostaglandins in rabbit gastric antral mucosa.
Effects of Fe(2+), Zn(2+), Cu(2+) and Se(4+) on the synthesis and catabolism of prostaglandins (PGs) in rabbit gastric antral mucosa were examined. Fe(2+) inhibited the cyclooxygenase activity in the microsomal fraction. Zn(2+) suppressed the endoperoxide E(2) isomerase activity in the microsomal fraction and the 15-hydroxy PG dehydrogenase (PGDH) activity in the cytosolic fraction. Cu(2+) stimulated the cyclooxygenase activity, inhibited the PGDH activity and possibly induced non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2 alpha) Se(4+) possibly induced the non-enzymatic reduction of PGG(2) or PGH(2) to PGF(2 alpha), as well as Cu(2+). These results suggest that Fe(2+), Zn(2+), Cu(2+) and Se(4+) can be modulators of the gastric antral mucosal PG levels by affecting the PG synthesizing enzymes, PG catabolizing enzyme and/or non-enzymatic reduction of PGG or PGH to PGF.
Animals↗
Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma.
The histogenesis of malignant fibrous histiocytoma (MFH) was studied using cisplatin (CDDP)-resistant MT-R8 and MT-R9 cells derived from cloned undifferentiated MT-8 and fibrohistiocytic MT-9 cells, respectively, which had been established from transplantable rat MFH. CDDP concentrations required for 50% suppression of proliferation of MT-R8 and MT-R9 cells were 5.4- and 3.3-fold greater than those of parental MT-8 and MT-9, respectively. MT-R8 and MT-R9 showed the higher positive rates to histiocytic lysosomal/ antigenic (ED1 and ED2) markers. The number of alpha-smooth muscle actin (SMA)-positive cells significantly increased in MT-R8; SMA-positive cells were also observed in MT-R9, but no difference was seen between MT-9 and MT-R9. MT-R8 and MT-R9 expressed both histiocytic and myofibroblastic phenotypes. However, the histology of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-R9 did not always reflect their in vitro nature. MT-R8 developed undifferentiated sarcomas similar to parental MT-8 tumors. In contrast, MT-R9 induced tumors with polytypic histologies such as the storiform growth pattern, neoplastic growth of granular cells and myofibroblasts, osteosarcoma-like areas, collagen-rich areas containing well-developed fibroblasts and areas involving many lipoblasts. These in vivo observations suggest the multidirectional differentiation of MT-R9 cells. Phenotypic modulation of rat MFH cells seemed to be easily induced by CDDP. A possible histogenesis of MFH was discussed based on the data collected.
Animals↗
A case of primary localized amyloidosis of the penile urethra.
Primary localized amyloidosis of the penile urethra is rare. We report a case in which the urethra was obstructed by amyloid tissue without evidence of systemic amyloidosis. After urethral dilatation, the patient reported a markedly improved urinary stream with minimal dysuria.
Aged↗
Assessment of indoor climate in an apartment by use of a fungal index.
Indoor climate was assessed in an apartment in Isehara City, Kanagawa Prefecture, Japan, by use of a fungal index. The index represents the environmental (climate) capacity to allow fungal growth; it is determined by measuring the growth rate of a biosensor fungus, Eurotium herbariorum J-183. Differences in climate among various parts of the apartment (microclimate) and its changes could be clarified by using the index. The index in the entire apartment was high in summer, low in winter, and intermediate in spring and autumn. According to the part of the apartment, the index was high in water-associated areas and cool areas. This high fungal index in cool areas was caused by the air at the same absolute humidity showing an increase in the relative humidity with a decrease in temperature. Fungal contamination rapidly progressed in areas with a high fungal index in this apartment. A correlation was observed between the fungal index and fungal contamination. Therefore, areas susceptible to fungal contamination can be estimated by use of the fungal index.
Air Microbiology↗
Phenotypic changes in lipopolysaccharide-treated cloned cells derived from transplantable rat malignant fibrous histiocytoma.
To investigate a possible phenotypic modulation, MT-8L and MT-9L cells were induced by in vitro culture of undifferentiated MT-8 and fibrohistiocytic MT-9 cells, which had been established from a rat malignant fibrous histiocytoma (MFH), in the medium containing 10 micrograms lipopolysaccharide (LPS)/ml. MT-8L and MT-9L gave greater positive reactions for histiocytic lysosomal markers and showed ultrastructures of histiocytic natures. In MT-8L, alpha-smooth muscle actin-positive myofibroblastic cells also significantly increased in number. MT-8L expressed both histiocytic and myofibroblastic phenotypes. MT-8L-induced tumors consisted mainly of storiform type MFH, differing from undifferentiated sarcoma type induced by MT-8. MT-9L and MT-9 tumors showed a storiform pattern. A phenotypic modulation of MFH cells was easily induced by LPS treatment.
Animals↗
Heterogeneity in the origin and immunophenotypes of "histiocytic" cells in transplantable rat malignant fibrous histiocytoma.
To clarify the origin and nature of "histiocytic" cells in malignant fibrous histiocytoma (MFH), immunoreactivities to rat macrophage/histiocyte-specific monoclonal antibodies (ED1 and ED2) and monocyte chemoattractant protein-1 (MCP-1) production were investigated using rat transplantable MFH-derived cloned cells (undifferentiated MT-8 and fibrohistiocytic MT-9). In different cultures, the positive rates for ED1 and ED2 ranged from 2.5% to 26.0% in MT-8, and from 6.0% to 40.0% in MT-9. In homotransplants, ED1-positive cells were frequently observed in MT-9 tumors, but barely seen in MT-8 tumors. In both MT-8 and MT-9 tumors, ED2-positive cells were not detected within tumors. Immunophenotypic characteristics of MT-8 and MT-9 to these antibodies seemed to be easily altered depending on in vitro and in vivo conditions. By ELISA, MCP-1 was hardly detected in culture supernatants of MT-8 and MT-9, but its level was very high in sera of MT-8- and MT-9-tumor-bearing rats. In rats with these tumors, the number of circulating monocytes was significantly increased and the presence of factors stimulating macrophage proliferation was demonstrated by the colony formation assay using rat bone marrow cells. Histiocytic cells in MT-8 and MT-9 tumors that were produced in nude mice reacted only with antibody to mouse macrophage-associated antigen. This suggests the existence of non-neoplastic, infiltrated macrophages of host origin that were induced probably by MCP-1 and factors stimulating macrophage proliferation. The present studies indicate the presence of heterogeneities in the origin and immunophenotypes of "histiocytic" cells in rat MFH.
Animals↗
Quantitative analyses of lesion areas of coronary atherosclerosis in cholesterol-fed rabbits.
A simple method to quantitatively evaluate atherosclerosis in the rabbit coronary arteries by measuring macroscopic lesion areas (%) was attempted in the present study. Sixteen rabbits were fed a 0.5% cholesterol diet for 15 weeks and then 9 rabbits were sacrificed whereas the remaining 7 rabbits were maintained for further 9 weeks on a normal chow (at week 24). The left circumflex coronary arteries (LCX) were excised from the rabbit hearts under stereoscopic observation. The prepared arterial strips of LCX were 38.7 +/- 7.1 mm long and all of them reached the cardiac apex from the orifice. At week 15, the lesion area in LCX was negligible (3.2 +/- 0.4%) whereas the aortic lesions significantly developed (50.0 +/- 7.6%). At week 24, atherosclerotic lesions in both LCX and aortas increased to 32.8 +/- 9.2% and 85.9 +/- 5.6%, respectively. This is the first report that determined the luminal surface areas of atherosclerotic lesions in rabbit coronary arteries. This method may be more practical and useful for quantitative evaluation of coronary atherosclerosis in a large number of rabbits than histological observations of serial sections of rabbit hearts.
Animals↗
Perivascular external granule cells in hereditary cerebellar vermis defect rat: pathogenesis of cerebellar cortical dysplasia.
Hereditary cerebellar vermis defect rats (CVD), a new neurological mutant, developed disorganized cerebellar cortical tissues. The postnatal development of the cerebellum in the CVD was examined histologically and immunohistochemically. A main pathological change in the CVD was abnormal perivascular cell aggregations, beginning to be observed from postnatal day 5. Around postnatal day 14, perivascular cells increased in number and many of them showed vigorous bromodeoxyuridine incorporation activities, as seen in the normal external granule cells (EGCs). The perivascular cells and EGCs were strongly positive for low affinity nerve growth factor receptor. These immunohistochemical results revealed that abnormal perivascular cells were heterotopic EGCs. The perivascular cells led to dysplastic abnormalities of lamination and abnormal cell positioning in the CVD. These findings indicate that abnormal perivascular aggregations of EGCs play an important role in the pathogenesis for cerebellar cortical dysplasia of CVD.
Animals↗
Disinfection of removable dentures using ozone.
Over time, removable dentures tend to become unsanitary and emit unpleasant odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused by denture plaque. Recently, various cleaning products designed to keep removable dentures sanitary have appeared on the market. It is known that denture plaque is mainly composed of Candida albicans (C. albicans), and that ozone seems to inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles (ozone concentration of about 10 ppm) was considered as clinically appropriate because of its strong disinfecting and deodorizing power, and high biological safeness. The effectiveness of this cleaner against C. albicans was investigated using. Results showed that C. albicans decreased to about 1/10 after 30 min and to 1/10(3) after 60 min.
Candida albicans↗
Lens development and crystallin distribution of the early onset hereditary cataract in the UPL rat.
The Upjohn Pharmaceuticals Limited (UPL) rat is a new dominant hereditary cataract model with two types of cataract formation, early onset (E-type) and late onset (L-type). In the UPL E-type rat cataracts have formed by the time the eyes open. The E-type rat also develops microphthalmos and buphthalmos. In this study, histological observations of cataract development in the E-type rats were performed during the period of fetal development, at birth and at 1, 3 and 62 weeks of age. In addition, the distribution of alpha- and gamma-crystallins in the developing lens was determined using anti-crystallin antisera. Abnormal elongation of the lens fibers was first observed on the 13th day of gestation. Stratification of lens epithelial cells was present on the 19th day of gestation and this change became more severe with age. There was no alteration in alpha- and gamma-crystallin expression during the fetal period. The continuity between the lens epithelial cells and lens fibers was lost at 3 weeks of age and it was assumed that differentiation of lens epithelial cells had ceased. These findings suggested that development of the UPL rat E-type cataract was related to an early abnormality in lens cell differentiation not involving crystallin expression.
Animals↗
Involvement of gicerin, a cell adhesion molecule, in tracheal development and regeneration.
Gicerin is a novel cell adhesion protein that belongs to the immunoglobulin superfamily. Gicerin protein adheres to neurite outgrowth factor, an extracellular matrix protein in the laminin family, and also exhibits homophilic adhesion. In the present study, we investigated the involvement of gicerin and neurite outgrowth factor in tracheal development and regeneration. In an early embryonic stage, gicerin protein was highly expressed in tracheal epithelial cells, but not in loosely arranged mesenchymal cells. During development, mesenchymal cells become condensed around the tracheal epithelium and then differentiate into muscle and cartilage; high levels of gicerin expression were observed in these cells. In the later embryonic and posthatching stages, no gicerin expression was detected in tracheal epithelium or cartilage. In addition, expression of gicerin increased transiently in the tracheal epithelium during the regeneration after tracheitis induced by the infectious bronchitis virus. Furthermore, a polyclonal antibody against gicerin inhibited the epithelial regeneration in tracheal organ cultures. These findings suggest that glcerin plays an important role in both tracheal development and regeneration.
Animals↗
Ex vivo gene delivery of platelet-derived growth factor increases 0-2A progenitors in adult rat spinal cord.
The O-2A progenitor cell, which serves as a stem cell for the myelinating oligodendrocyte, has been implicated as a major target for radiation-induced spinal cord injury. In an attempt to increase the number of O-2A cells in the spinal cord, we applied an ex vivo gene therapy procedure for delivering platelet derived growth factor (PDGF). Recombinant fibroblasts expressing PDGF A chain were injected into the cisterna magna of adult rats, which resulted in cell seeding of the subarachnoid space of the cervical spinal cord. The number of O-2A progenitors in the cervical spinal cord was then assessed with an in vitro clonogenic assay. O-2A cells were found to be increased 8 days after recombinant cell injection, and they remained elevated up to at least 14 days. Analysis of O-2A colonies indicated that the implantation of PDGF-expressing cells increased the number of O-2A progenitors without affecting their in vitro proliferation potential or differentiation capacity. These data suggest that implantation of PDGF-expressing cells in the subarachnoid space of the cervical spinal cord may influence a stem cell population critical to the repair of demyelinated lesions.
Animals↗