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Biomedical subjects

K Toyoshima

Publications and source records attributed to K Toyoshima.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Factors aggravating bronchial asthma in urban children (I)--The involvement of indoor air pollution].

The aggravation of bronchial asthma in today's urban child population was studied by an epidemiological study in order to elucidate the involvement of indoor air pollution in relation to housing style. The asthma group consisted of 210 children under 12 years old who had been recently diagnosed as having bronchial asthma and under the care of Osaka Prefectural Habikino Hospital. The non-asthma group consisted of 180 children under 12 years old who had been under care at Osaka Prefectural Hospital but had no present history of allergic symptom. The individual atmospheric environment and housing style were surveyed by questionnaire. Also, the amount of mite allergen (Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae) in room and bedding dust and the concentration of cotinine in urine were examined as objective indicators for the load of environmental allergen and the indoor air pollution by tobacco smoke, respectively. In this study, bronchial asthma was classified into two types: atopic/non-atopic, according to whether Dp-specific immunoglobulin E (Dp-IgE) was present/absent (positive/negative). Thus, for the risk factors given above, their involvement in each type of asthma was examined by comparing the proportion of the exposed subjects between the three groups of atopic asthma, non-atopic asthma and non-asthma. As atopy is an important factor of child asthma, the relative risk (odds ratio) of Dp-IgE increase (atopy) was also determined for the same factors by logistic regression analysis in each of the asthma and non-asthma groups. The results are as follows: 1. Reinforced concrete housing material, which results in mal-ventilation, increased the load of indoor air pollutants such as tobacco smoke. 2. A higher amount of mite allergen in bedding dust increased Dp-IgE. 3. Heating with stove, which results in a higher room humidity as well as temperature, enhanced Dp proliferation and appeared to be involved in increasing the risk of atopic asthma. 4. Reinforced concrete housing material appeared to be involved in suppressing Dp-IgE and increasing the risk of non-atopic asthma. But some air pollutants such as tobacco smoke and mite allergen showed no relationship to these involvements.

Air Pollution, Indoor↗
PubMed1998

[Factors aggravating bronchial asthma in urban children (II)--The involvement of atopy and serum fatty acids, and their interaction with urban living environment].

The aggravation of bronchial asthma in today's urban child population was studied by an epidemiological study in order to elucidate the involvement of food habits as well as individual factors such as age, sex, and history of atopic dermatitis, and the interaction with urban living environments. The asthma group consisted of 202 children under 12 years old who had been recently diagnosed as having bronchial asthma and under the care of Osaka Prefectural Habikino Hospital. The non-asthma group consisted of 81 children under 12 years old who had been under care at Osaka Prefectural Hospital but had no present history of allergic symptom. The individual factors and the urban living environments (atmospheric environment, housing style) were surveyed by questionnaire. Also, the mite (Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae) specific immunoglobulin E (Dp-IgE, Df-IgE) and the composition of serum fatty acid were examined as objective indicators for atopy and dietary habits, respectively. In this study, bronchial asthma was classified into two types: atopic/non-atopic, according to whether Dp-IgE was present/absent (positive/negative). Thus, for the risk factors given above, their involvement in each type of asthma was examined. As atopy is an important factor of child asthma, the relative risk (odds ratio) of Dp-IgE increase (atopy) was also examined by logistic regression analysis in each of the asthma and non-asthma groups. The results are as follows: 1. As age increased, the risk of atopy increased but the risk of asthma decreased. 2. The risk of asthma increased as Dp-IgE rather than Df-IgE increased. 3. For the composition of serum fatty acid, the lower quartile ranking (LQR) group for a saturated fatty acid, stearic acid, and the upper quartile ranking (UQR) group for a mono-unsaturated fatty acid, oleic acid, had a higher risk of nonatopic asthma. 4. The LQR group for omega 6-poly-unsaturated fatty acid such as linoleic acid, had a lower risk of atopy. 5. The UQR group for a omega 3-poly-unsaturated fatty acid, eicosapentaenoic acid, had a higher risk of nonatopic asthma. The UQR of eicosapentaenoic acid and living environments within 25 m from a major road or housing of reinforced concrete structure showed involvement in synergistic increase in the risk of non-atopic asthma.

Asthma↗
PubMed1998

[Tuberculosis in children].

Newly registered active tuberculosis in children is under 300 persons a year in Japan, now. In order to lessen further and exterminate childhood tuberculosis in near future, physician have to make effort to find the infected children by good-timing thorough surveillance when he find an adult tuberculosis patient. Chemoprophylaxis could prevent the infected children from progressing to active disease. BCG vaccination in infantile period is still important in Japan, especially to protect young children from disseminated tuberculosis. Pulmonary tuberculosis in children is successfully treated with 6 months standard multi-drugs therapy.

Child↗
PubMed1997

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Adenomatous Polyposis Coli↗
PubMed1997

Keratinocytes become terminally differentiated in a process involving programmed cell death.

Oral keratinocytes originate from basal cells, differentiate during migration to the surface, and finally are shed. Apoptosis occurs at the end of differentiation, but the precise relationship between terminal differentiation and apoptosis is not clear. In the present study, Bcl-xL was expressed in the basal cell and spinous cell layers, and Bax was expressed in the spinous cell and granular cell layers. In cultured keratinocytes, Bcl-xL was expressed under conditions of 0.1 mM calcium (low Ca2+) but disappeared under conditions of 1.0 mM calcium (high Ca2+); the latter induces keratinocyte differentiation. Bax was not expressed in keratinocytes with low Ca2+ but was expressed in cells with high Ca2+. Finally keratinocytes with high Ca2+ underwent apoptosis, which was detected by the TUNEL method and by 180-bp DNA fragmentation. These results suggest that the process of terminal differentiation in gingival epithelium is a pathway to apoptosis.

Apoptosis↗
PubMed1997

K-ras is essential for the development of the mouse embryo.

ras genes encode members of the small GTP-binding proteins. Ras protein in highly conserved in various species from yeast to humans and plays a key role in signal transduction. Ras is related to cell proliferation and differentiation. While, in addition, mutations in the ras genes are implicated in a variety of tumors. However, the physiological functions and specific roles of each ras gene, H-ras, K-ras and N-ras, are still not fully understood. To clarify the role of the K-Ras in vivo, we generated K-ras mutant mice by gene targeting. In contrast to the findings that H-Ras-deficient mice and N-Ras-deficient mice are born and grow normally, the K-Ras-deficient embryos die progressively between embryonic day 12.5 and term. At embryonic day 15.5, their ventricular walls are extremely thin. Besides, at embryonic day 11.5, they demonstrate increased cell death of motoneurons in the medulla and the cervical spinal cord. Our results thus indicate K-Ras to be essential for normal development in mice and residual Ras composed of H-Ras and N-Ras cannot compensate for the loss of K-Ras function in the mutant mice.

Animals↗
PubMed1997

Identification of a novel nuclear localization signal in Sam68.

Sam68, a nuclear RNA binding protein, binds to Src and is phosphorylated at tyrosine residues in an M-phase specific manner. Here we identified a stretch of 24 amino acid residues in the COOH-terminal portion of Sam68 which function as a nuclear localization signal. This signal sequence bears no apparent homology to any other known nuclear localization sequence. However, this sequence was found to contain a motif, PPXXR (P, Pro; R, Arg), which is conserved in various RNA binding proteins including hnRNP proteins. Replacement of Arg in this motif with Ala abolished the nuclear accumulation of a GFP fusion protein, suggesting that this residue is important in translocating the protein to the nucleus.

3T3 Cells↗
PubMed1997

The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells.

WT1 was isolated as a tumor suppressor gene of Wilms tumor. However, high expression of WT1 correlates with poor prognosis in acute leukemia. In addition suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells, suggesting that WT1 is important for their proliferation. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the isopropyl-beta-D-thiogalactoside (IPTG)-controlled expression system. We found that induction of one splicing variant of WT1 [WT1-17AA(+)-KTS(-)] in M1 cells induces cell cycle arrest and apoptotic cell death. These results suggest that the role of WT1 is different depending on the type of leukemia cell in which it is expressed.

Animals↗
PubMed1997

Isolation, partial purification, and ultrastructure of taste bud cells from rabbit foliate papillae.

A method is described for obtaining large numbers of isolated taste bud cells from lingual epithelium of rabbit foliate papillae. The isolation method is based on isopyenic sedimentation in a Percoll gradient. The purification of taste bud cells was evaluated by electron microscopy and by immunohistochemistry using CK 20 antibody. The cytology of the isolated taste bud cells remained very similar to in situ cells. The type III cells, which are regarded as gustatory cells, retained their characteristic dense-cored granules in the cytoplasm. This method will permit study of various parameters of taste bud cell biology.

Animals↗
PubMed1997

Ultrastructure of the salivary glands in the midtongue of the common vampire bat, Desmodus rotundus.

BACKGROUND: All examined mammals have at least two sets of lingual salivary glands: von Ebner's glands and Weber's glands. A third set, the glands of Blandin and Nuhn, is present in the tongues of some but not all mammals. Vampire bats, Desmodus rotundus, are unusual in that they possess another set of lingual glands, these being in the midtongue region. METHODS: The anterior half of the tongue was extirpated from several adult vampire bats, dissected, and tissue blocks derived from the midregions of the body of the tongue prepared for transmission electron microscopy by conventional means. RESULTS: The midlingual glands are in the form of long, tubular secretory endpieces that are succeeded by ducts of simple morphology. In general, the secretory portions consist of two cell types, which may be intermingled in the same tubule or may form tubules that consist wholly of one cell type or the other. Seromucous cells usually have one or several rough endoplasmic reticulum cisternae that are hugely distended by a homogeneously dense material. Their granules have a bizonal substructure: one or several dense bands are embedded in a lighter matrix. Mucous cells are rather typical in structure, but their secretory product is different from run-of-the-mill mucous droplets. These droplets vary in density from cell to cell. In some cells, these droplets have a relatively light matrix; in other cells, the droplet is unusually dense, consisting mainly of a dark, structureless matrix with marginal lenticular lacunae of low density in which some short, irregular filaments are scattered. A rare finding is the presence of ciliated cells intermingled with secretory endpiece cells. The cilia are of conventional morphology. Secretory tubules are succeeded by ducts that resemble intercalated ducts; the epithelium of these ducts gradually increases in height to form a kind of excretory duct, without the intervention of striated ducts. As the ducts approach the lingual surface, the epithelium changes to stratified squamous. CONCLUSIONS: Saliva produced by the midlingual glands may be an aid in the reciprocal grooming behavior of vampire bats. Based on their morphology, the excurrent ducts may not modify the initial saliva elaborated by these glands and might act simply as pipelines by which the saliva reaches the mouth.

Animals↗
PubMed1997

The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle.

In order to investigate the subnuclear interactions of the WT1 gene product, nuclear fractionation analyses were performed with human osteosarcoma HOS and myelogenous leukemia K562 cells. The WT1 protein was tightly associated with the nucleus and was resistant to high-salt or detergent extraction and DNase I digestion. Both the expression level and stability of WT1 and its resistance to high salt and DNase I treatments remained constant during the cell cycle. In addition, human WT1 ectopically expressed in mouse NIH3T3 cells was also resistant to these treatments. These results suggest that WT1 functions in tight association with the nuclear matrix.

3T3 Cells↗
PubMed1997

DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95.

BACKGROUND: The human homologue of the Drosophila discs large tumour suppressor protein (hDLG) and closely related proteins such as postsynaptic density protein 95 kDa (PSD-95) are associated with N-methyl-D-aspartate receptors (NMDA-R) and Shaker-type K+ channels, and are thought to be involved in their clustering. RESULTS: We have identified a protein named DAP-1 that binds to the guanylate kinase-like domains of hDLG and PSD-95. DAP-1 was found to associate with hDLG, PSD-95, NMDA-R and adenomatous polyposis coli protein (APC). Furthermore, we found that DAP-1 is specifically expressed in the brain and colocalizes with PSD-95 and APC in mouse cerebellum. We also found that DAP-1 is colocalized with PSD-95 and NMDA-R at the synapses in cultured rat hippocampal neurons. CONCLUSION: Our findings suggest that DAP-1 may play several roles in the molecular organization of synapses and neuronal cell signalling by interacting with hDLG and PSD-95, which in turn are associated with receptors, ion channels and APC.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Immunohistochemical demonstration of bcl-2 protein in ameloblastoma.

The bcl-2 gene is known through its product, bcl-2 protein, which prevents apoptosis, and also by its expression in development, especially in sites characterized by epithelial-mesenchymal interactions. In the developing tooth germ, bcl-2-protein is expressed in the epithelial component. In this study, we examined the expression of bcl-2 protein immunohistochemically in 25 ameloblastomas using a monoclonal antibody against anti-human bcl-2 oncoprotein. In all 25 cases, bcl-2 protein was found mainly in the outer layer of tumor cells, whereas the inner cells (stellate reticulum-like cells and squamoid cells) were negative. The bcl-2 protein is therefore thought to play a role in maintaining the stem-cell population in the peripheral layers of the tumor nests from which proliferating cells can be recruited.

Adolescent↗
PubMed1997

Ultrastructure of the parotid gland in the common vampire bat, Desmodus rotundus, with special emphasis on oncocytes.

The parotid gland of the common vampire bat, Desmodus rotundus, is a pure seromucous gland. Typical acinar cells have a complement of secretory granules with a light matrix and one or several spherules and ancillary densities. These cells also contain mitochondria of conventional appearance. Mixed in with these acinar cells are cells that fulfil all of the ultrastructural criteria for identification as oncocytes. They contain enhanced numbers of mitochondria that frequently display peculiarities in the number and disposition of their cristae. The oncocyte mitochondria are closely packed and often are joined by periodic bridges. Most of the cells in the intercalated ducts are cytologically unremarkable; a few scattered duct cells have a single, grossly distended cisterna of rough endoplasmic reticulum that contains a homogeneous material of moderate density. The intercalated ducts are succeeded by ducts that lack the usual basal striations, but that consist of cells with numerous, small, dense granules. These secretory ducts probably are the homologues of striated ducts in parotid glands of other species. The structure of these ducts in the parotid gland in the vampire bat suggests that this gland does not play a homeostatic role in the regulation of electrolytes, a role that appears to be carried out in this bat in the submandibular glands, but that its major intralobular ducts contribute substantial quantities of organic material to the saliva.

Animals↗
PubMed1996

Constitutive expression of the Wilms tumor suppressor gene WT1 in F9 embryonal carcinoma cells induces apoptotic cell death in response to retinoic acid.

The product of the Wilms tumor suppressor gene, WT1, is thought to be a tissue specific transcription factor regulating cell growth and differentiation. To elucidate the function of WT1 in cellular differentiation, we examined the changes in the level of WT1 expression during retinoic acid induced-differentiation of embryonal carcinoma F9 cells into parietal endoderm cells. We found that, in response to retinoic acid addition, the expression of WT1 increased significantly after 12--24 h of incubation, then decreased and finally disappeared after 4 days, by which time most of the cells had differentiated into primitive endoderm cells. To examine the significance of these changes in WT1 expression, we established cell lines constitutively expressing one of the WT1 splicing variants. These cell lines showed a phenotype very similar to parental F9 cells in the absence of retinoic acid. However, in the presence of retinoic acid, they failed to differentiate into primitive endoderm cells and underwent apoptotic death 36 h after the addition of retinoic acid. These results suggest that downregulation of WT1 expression is necessary for normal differentiation of F9 cells into parietal endoderm cells.

3T3 Cells↗
PubMed1996

Calcineurin is essential for DNA synthesis in Swiss 3T3 fibroblasts.

DNA synthesis was measured 16 h after stimulation of Swiss 3T3 fibroblasts in the resting phase with various growth factors (platelet-derived growth factor, fibroblast growth factor, lysophosphatidic acid and thrombin). When extracellular Ca2+ was chelated by EGTA, or when the influx of Ca2+ from outside to inside the cell was blocked by cobalt, DNA synthesis was completely inhibited. As there was no effect whatsoever on DNA synthesis when Ca2+ was chelated, or when the influx of Ca2+ was blocked up to the first 4 h after growth stimulation, it was concluded that, at an early stage, Ca2+ influx from outside to inside the cell is not related to the transition from the G1 to the S phase. A Ca2+/calmodulin-dependent protein kinase II inhibitor (KN-62) had no effect on DNA synthesis. However, cyclosporin A and FK-506, which are inhibitors of Ca2+/calmodulin-dependent protein phosphatase 2B (calcineurin), markedly inhibited DNA synthesis stimulated by all of the growth factors. These results indicate that calcineurin plays a role, not only in activation of T-cells of the immune system in the initial phase, but also in DNA synthesis in fibroblasts. It was concluded that Ca2+ influx from outside to inside the cell during the mid-to-late G1 phase, followed by calcineurin activation, is essential as a mechanism of growth signal transduction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Upregulation of the APC gene product during neuronal differentiation of rat pheochromocytoma PC12 cells.

The adenomatous polyposis coli (APC) gene, the mutation of which is responsible for familial adenomatous polyposis and sporadic colorectal tumors, is highly expressed in the central nervous system. To elucidate the contribution of the APC protein to neuronal differentiation, changes in APC expression were examined during nerve growth factor (NGF)-induced differentiation of rat pheochromocytoma PC12 cells. The expression of APC gradually increased throughout the time course, in particular it increased markedly after 7 days of exposure to NGF. However, forced expression of APC did not induce neuronal differentiation of PC12 cells. These results suggest that the APC protein itself does not have the potential to induce neuronal differentiation, but rather is upregulated secondary to the differentiation of PC12 cells.

Adenomatous Polyposis Coli Protein↗