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Biomedical subjects

K Toyoshima

Publications and source records attributed to K Toyoshima.

At least 109 records · Page 6Linked to original sources

Symbiotic bacteria in the accessory submandibular gland of the club-footed bat, Tylonycteris pachypus.

The lumina of the secretory endpieces and, to a lesser extent, of the duct system of the accessory submandibular gland of the club-footed bat, Tylonycteris pachypus, contain numerous rod shaped bacteria. Despite their abundance, these microbes do not evoke an inflammatory response by the glands. The major submandibular gland, as well as the other major salivary glands in these exotic animals contain no bacteria whatsoever. It is concluded that the bacteria in the accessory submandibular gland are symbionts, and that they may play a role in digestion or in the social behavior of their host organisms.

Animals↗

Identification of the cells expressing cot proto-oncogene mRNA.

The cell types expressing cot proto-oncogene mRNA were identified by in situ hybridization (ISH) histochemistry. Among a variety of adult mouse tissues examined, four types of glandular cells expressing cot gene were identified: (1) granular duct cells in the submandibular and sublingual glands; (2) serous cells in the parotid gland; (3) peptic (chief) cells in gastric glands; and (4) goblet cells in colonic glands. Investigation of the developmentally regulated expression of cot mRNA using tissues of 14-day and 18-day embryos, newborn and weanling mice showed that cot gene is expressed only in morphologically differentiated and functionally activated cells of these four types. No other types of cells showing ISH signals were observed. Based on these results, cot gene expressions in cultured cells of colonic adenocarcinomas and gastric adenocarcinomas were examined. SW 480 and WiDr cells showed high expression of this gene and so should be useful for functional analysis of Cot kinase. The expression patterns of cot gene in tumor tissues of the parotid gland, and gastric and colonic glands were investigated. Two of the tissues overexpressed this gene markedly, suggesting that overproduction of Cot kinase may be one cause of their transformation.

Adenocarcinoma↗

[Effects of inhaled beclomethasone on height growth and bone metabolism in children with asthma].

To evaluate the influences of inhaled beclomethasone dipropionate (BDP), 7.3-30.9 (15.5 +/- 6.5) micrograms/kg/day, on bone metabolism and height growth, we performed a longitudinal study for 6 months in 34 children with asthma aged between 3 and 15 years. Bone mineral density estimated by digital image processing method (DIP) and serum level of osteocalcin did not show any significant change, but height growth was slightly suppressed in the patients who inhaled more than 15 micrograms/kg/day of BDP. We concluded that the decision to prescribe inhaled BDP should be made on the balance of the clinical effects and the improvement of quality of life against the possibility of side effects.

Administration, Inhalation↗

Platelet-activating factor. Role in fetal lung development and relationship to normal and premature labor.

In this overview on the role of PAF in reproductive biology, we have emphasized its relationship to fetal lung maturation and the initiation and maintenance of parturition. In addition, we have discussed the role of this autacoid in certain complications of premature delivery. It should be pointed out, however, that it is our view that other mediators and cytokines also play a role in these processes. In the past, many investigators have suggested a central role for one of these mediators that serves as the "trigger" of these biologic events. It is our view that these systems are regulated by a number of effectors, among which PAF may play an important role.

Cytokines↗

[The current situations and measures in the future in childhood tuberculosis].

We performed a retrospective analysis of 358 patients who were treated for active TB in our hospital from 1976 to 1993. The rate of primary pulmonary tuberculosis was 49.0% and post primary pulmonary tuberculosis was 25.6%. But the rate of tuberculous meningitis and miliary tuberculosis was 7% respectively. Fatal cases of tuberculous meningitis had continued. Seventy-four percent out of 358 patients had a contact history with active tuberculosis. Main source of infection were their father, mother and grandparents. Thirty-two percent of patients had received BCG. Only 12.6% out of the patients under 5 years of age had received BCG. Only nine percent of 23 cases with tuberculous meningitis had received BCG. If the Ministry of Health and Welfare criteria of chemoprophylaxis was indicated rigidly, about 40% of patients who needed chemoprophylaxis in this study would have been overlooked. Indication of chemoprophylaxis should be decided in each patient flexibly. The study of the contact examination showed that two thirds toddler had tuberculosis within two months after detection of source of infection. Thirty percent of the patients in this study were preventable if contact examination and chemoprophylaxis were appropriately done. In the study of drug susceptibility of TB bacilli from 71 patients, 14 strains were resistant to at least one drug. The resistant rate to each drug was higher than adult resistant rate. In order to eliminate childhood TB, the following is necessary: 1) BCG vaccination in the early infancy. 2) prompt and appropriate contact examination and chemoprophylaxis, 3) infection control against drug resistant bacilli.

Adolescent↗

[Assessment of effectiveness of BCG vaccination against childhood tuberculosis].

We performed a retrospective analysis of the history of BCG vaccination of 367 childhood patients who were treated for active tuberculosis (TB) in our hospital from 1976 to 1994. Fifty-eight percent of 367 cases, 83.1% of cases under 5 years of age and 92% of tuberculous meningitis had not received BCG. To investigate the effectiveness of BCG vaccination against TB, we carried out case-control studies using 59 patients with TB and 118 controls without TB. The cases were patients treated for TB in our hospital from 1988 through Nov. 1994. Two controls were chosen for every case with matching for sex, age at admission, year of admission and place of residence. Based on whole 59 pairs, BCG vaccination was shown to have protective efficacy of 78% (95% confidence interval [CI], 57-89%). For 34 pairs of under 5 years of age, estimated efficacy was 92% (95%CI, 80-97%), for primary pulmonary disease (27 pairs) it was 92% (95%CI, 78-97%). For bacteriologically confirmed TB (27 pairs), it was 84% (95%CI, 58-94%), while for bacterilogically negative TB (32 pairs) 71% (95%CI, 27-89%). Our results indicate that BCG vaccination with multipuncture methold protected considerably against TB in infants including primary pulmonary TB.

Adolescent↗

Serum-independent phosphorylation of c-Jun and alterations in AP-1 components by transformation with various oncogenes.

To understand the mechanisms regulating the transactivating activity of Jun/AP-1, we analyzed alterations in c-Jun induced by growth stimulation and cell transformation. Serum stimulation of quiescent NIH3T3 cells induced a marked increase in phosphorylation of c-Jun in its amino-terminal activation domain. On the other hand, this domain was highly phosphorylated, in a serum-independent manner, in cells transformed with various oncogenes, including active c-raf-1, v-src, active Ha-ras, and active erbB-2. There were no obvious differences in the phosphorylation states of c-Jun in exponentially growing normal and transformed cells. However, in the exponentially growing state, the TRECAT activity in transformed cells was markedly higher than that in normal cells. Gel retardation analysis indicated that the AP-1 components in transformed cells were significantly different from those in normal cells. These results suggest that some other alterations besides phosphorylation of c-Jun are involved in enhancement of AP-1 activity in exponentially growing transformed cells.

3T3 Cells↗

Coenzyme A-independent transacylation in amnion-derived (WISH) cells.

Total membranes or microsomal fractions prepared from the amnion-derived WISH cell line posses a coenzyme A-independent transacylase activity. The transacylase utilizes 1-alkenyl- and 1-alkyl-2-lysoglycerophospholipids as preferred acceptors. Marginal transacylation was observed with 1-acyl-2-lysoglycerophospholipids. The reaction occurred in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and was not affected by phospholipase A2 inhibitors. Both 1-acyl- or 1-alkyl-glycerophosphocholines containing an arachidonoyl residue in the sn-2 position were effective as donors, while 2-oleoyl- or 2-palmitoyl-glycerophosphocholines were ineffective. The presence of the transacylase, the specificity of the substrates, and the stability of the 1-alkenyl bond provide a biochemical model that may explain the increased proportion of a highly enriched arachidonate-containing phosphatidyl-ethanolamine-plasmalogens fraction that is found in amnion at term.

Acylation↗

Structure and physiological properties of the taste organs on the ventral side of frog tongue (Rana catesbeiana).

The structure and physiological properties of the non-papillary taste organs on the ventral side of frog tongue were examined. The taste organs were distributed around the hyoglossal muscle of the tongue. The total number of organs was estimated as about 100. The fine structure of the taste organs was similar to that of the fungiform papilla. Neural responses recorded from the glossopharyngeal nerve by applying chemical stimuli to the ventral side of the tongue were noticeably smaller than those to the dorsal side of the tongue. The taste cells on the ventral side of the tongue generated receptor potentials to various chemical stimuli like those on the dorsal side of the tongue.

Animals↗

Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system.

The Src-like protein-tyrosine kinase Fyn is associated with T-cell antigen receptor. Transient expression of actively mutated Fyn, having Phe-528 instead of Tyr-528 or Thr-338 instead of Ile-338, in Jurkat T-cells stimulated the serum response element (SRE), 12-O-tetradecanoyl-phorbol-13-acetate response element, cyclic AMP response element, and c-fos promoter. The stimulation of SRE was particularly prominent not only with active Fyn but also with normal (wild-type) Fyn. SRE was also stimulated by both normal and active Lck. Furthermore, normal and active Fyn stimulated transcription from the IL-2 gene promoter when transfected cells were stimulated by concanavalin A plus 12-O-tetradecanoylphorbol-13-acetate. Under the same conditions, Lck did not stimulate IL-2 promoter unless it was activated by mutation. Interestingly, a mutant Fyn, which has deletions within the SH2 region and so is able to transform chicken embryo fibroblasts, did not stimulate either the c-fos or IL-2 promoter, suggesting the importance of this region in T-cell signaling. Csk, which phosphorylates tyrosine residues in the negative regulatory sites of Src family kinases, down-regulated Fyn- and Lck-mediated stimulation of the serum response element and Fyn-mediated enhancement of IL-2 promoter activity. These data suggest that Fyn and Lck, whose activities are regulated by Csk, are involved in different phases of T-cell activation.

Amino Acid Sequence↗

17 beta-estradiol mimics ligand activity of the c-erbB2 protooncogene product.

We report here the physical and functional interaction of estrogen with the ErbB2 protein p185c-erbB2. The ErbB2 protein immunoprecipitated from estrogen-treated [10(-8) to 10(-6) M 17 beta-estradiol (E2)] RC cells showed higher autophosphorylation activity than that from untreated cells. Likewise autophosphorylation activity of ErbB2 protein from untreated cells was stimulated in vitro by E2. In addition, E2 treatment induced down-regulation of ErbB2 protein from the detergent-soluble fraction of the RC cells within 15 min. E2 also induced morphological transformation of the RC cells but not of the parental NIH 3T3 cells, which express little c-erbB2 under the same experimental conditions. This morphological transformation of RC cells was reversed by tamoxifen. However, E2 treatment did not induce anchorage-independent growth of RC cells. Scatchard analysis revealed E2 binding to the ErbB2 protein on RC cells; the Kd value was 2.7 nM. E2 did not bind appreciably to the parental NIH 3T3 cells or cells expressing an ErbB2 protein lacking most of its extracellular domain. These data suggest that estrogen plays an important role in ErbB2-mediated signaling.

3T3 Cells↗

Metabolism of hexadecanol by rat type II pneumonocytes.

Type II pneumonocytes isolated from adult rats incorporate radioactivity from 1-[3H]hexadecanol into either lipids. The radioactivity is distributed between the neutral lipids, phosphatidylcholines, and phosphatidylethanolamines. The neutral lipid fraction is almost exclusively composed of triradylglycerols. The potent ether-containing glycerophospholipid, platelet-activating factor, has been shown to stimulate glycogen breakdown and surfactant secretion. In consideration that a long chain alcohol (hexadecanol) is added to certain artificial surfactant preparations which are utilized in the treatment of respiratory distress syndrome of the newborn, the metabolism of hexadecanol by the type II pneumonocytes should be taken into account.

Animals↗

The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation.

The cot gene is an oncogene encoding serine/threonine kinases isolated by DNA transfection assay. In this study, we isolated cDNA for the human cot protooncogene (proto-cot gene) and examined the structure and function of its gene products. The proto-cot gene has an open reading frame encoding 467 amino acids of which the first 397 amino acids are identical to those in the corresponding part of the cot gene. The protein products of the proto-cot gene were identified as 58- and 52-kDa proteins with intrinsic protein serine/threonine kinase activity. These two protein species were suggested to be generated by alternative initiation from two AUGs. The 58- and 52-kDa proteins are both localized predominantly in the cytosol, but the 58-kDa protein has a shorter half-life than the 52-kDa protein, suggesting the importance of the amino-terminal domain in regulating the stability of the proto-Cot protein. More interestingly, the 58-kDa protein showed stronger transforming activity than the 52-kDa protein, although this activity was much weaker than that of the Cot oncoprotein. Thus, the amino-terminal domain of the Cot protein may be necessary for cellular transformation, whereas the carboxyl-terminal domain may negatively regulate the transforming activity.

Amino Acid Sequence↗

Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils.

The interaction of Fc receptors with antibody-antigen complexes activates multiple biological functions in hematopoietic cells. Recently, protein-tyrosine phosphorylation has been suggested to be involved in Fc receptor-mediated cell signaling. Here we show that the Src-like protein-tyrosine kinase Fgr, which is specifically expressed in mature myelomonocytic cells, coimmunoprecipitates with IgG Fc receptor II (Fc gamma RII), but not with Fc gamma RIII from detergent lysates of human peripheral neutrophils. Crosslinking of Fc gamma RII induced a rapid increase in the tyrosine kinase activity and comodulation of Fgr. These results suggest that Fgr is physically and functionally associated with Fc gamma RII and involved in Fc gamma RII-mediated signal transduction pathways.

Animals↗

Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.

Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or inhibition of their growth. The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins and rapid activation of Src-like kinases. The amino acid sequences of five proteolytic peptides of p75, a major substrate of protein-tyrosine(s) in the signaling, showed that p75 is the human HS1 gene product. The HS1 gene is expressed specifically in hematopoietic cells and encodes p75HS1, which carries both helix-turn-helix and Src homology 3 motifs. p75HS1 showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinases upon B-cell antigen receptor-mediated signaling.

Adaptor Proteins, Signal Transducing↗

Effect of anticardiolipin antibody in patients with recurrent fetal loss on thrombomodulin-dependent protein C activation.

In order to approach an understanding of the mechanisms of fetal death in patients with antiphospholipid syndrome we investigated the association between protein C activity and anticardiolipin antibody. Protein C activity in vivo was decreased in some patients with recurrent fetal loss and a high ACA titer. This study suggests that anticardiolipin antibody in patients with recurrent fetal loss may inhibit activation of protein C by thrombomodulin.

Abortion, Habitual↗

Fine structure of Merkel corpuscles in the lingual mucosa of Japanese quail, Coturnix coturnix japonica.

By electron microscopy, these corpuscles were found exclusively in the connective tissue just beneath the dorsal epithelium near the lateral margin of the tongue. Each consisted of 4-8 Merkel cells and flattened nerve terminals arranged alternately. The Merkel cell was characterized by dense-cored granules, with a diameter ranging from 120 to 180 nm, throughout the cytoplasm. The functional significance of the avian Merkel cell, i.e. a mechanoreceptor cell or a trophic cell with the axon, still remains enigmatic, as is the case with Merkel cells of other vertebrates.

Animals↗