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Biomedical subjects

S Tsukada

Publications and source records attributed to S Tsukada.

At least 73 records · Page 4Linked to original sources
PubMed1995

Follow-up study of patients treated for ingrown nails with the nail matrix phenolization method.

In the past 7 years, a total of 537 ingrown nail lesions were treated with the nail matrix phenolization method (NMP). A study was performed based on follow-up examinations and a questionnaire survey regarding recurrence rate, degree severity, duration of postoperative pain, and other relevant factors. The major advantages of the NMP revealed by our study were: (1) The surgical procedure is easy to perform and does not require specialized equipment; (2) total time requirement for surgery is minimal; (3) the operation can be performed in the presence of a concomitant infection; (4) the recurrence rate is low (1.1%); and (5) postoperative pain and postoperative bed rest is minimized. These results indicate that NMP is an extremely effective method for treatment of ingrown nails.

Adolescent↗
PubMed1995

Effects of probenecid and cimetidine on the renal excretion of 3'-azido-3'-deoxythymidine in rats.

The mechanisms underlying the inhibitory effects exerted by probenecid and cimetidine on the renal excretion of 3'-azido-3'-deoxythymidine (AZT) were investigated in rats in vivo. On i.v. administration, the findings indicated that both probenecid and cimetidine increased the plasma concentration of AZT and inhibited its renal excretion. To clarify the mechanisms underlying the interaction of these drugs with AZT and to elucidate the process of renal secretion of AZT, further investigation was performed, in which [3H]AZT (0.5 microM) was injected rapidly into the right renal artery, and its outflow profile from the right ureter was compared with that from the left ureter. In control experiments, 56.6% of the administered AZT was secreted from the right kidney, and it was calculated that the transcellular transit time of AZT in this process was 0.30 min. In the presence of 10 mM probenecid and of 10 mM cimetidine, the secretion of AZT was reduced to 15.3 and 32.3%, respectively, the inhibition induced by probenecid being more effective than that induced by cimetidine. However, the transcellular transit time of AZT increased to 0.53 and 1.21 min in the probenecid and cimetidine studies, respectively. Thus, cimetidine was more potent than probenecid in its effects on the transit time. These findings indicate that probenecid and cimetidine affect different steps in the renal secretion of AZT. It was therefore concluded that, on the renal plasma membrane, AZT is transported by anion transport systems, whereas on the brush border membrane, AZT is secreted by cation transport systems.

Animals↗
PubMed1994

Hepatocyte growth factor region specifically stimulates gastro-intestinal epithelial growth in primary culture.

Hepatocyte growth factor (HGF) stimulated the growth of fetal rat gastrointestinal epithelial cells in primary culture with a clear dose-response relationship. The epithelial response to the mitogenic activity of HGF was different among the region of the gastro-intestinal tract; glandular stomach most responsive, followed by intestine and forestomach. The interaction of HGF with other growth factors in inducing the epithelial growth was also different depending on the type of the epithelial cells, indicating a region-specific growth regulation in the gastro-intestinal tract. Analyses using Northern blot and RT-PCR revealed that HGF mRNA was expressed only in mesenchymes but not in epithelia of the gastro-intestinal tract while expression of c-met (HGF receptor) gene was observed in both tissues. These results suggest that gastro-intestinal mesenchymes secrete HGF which stimulates the growth of attaching epithelial cells by a paracrine mechanism, and that the epithelial response to HGF is controlled by a region-specific growth regulatory mechanism.

Animals↗
PubMed1994

IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and Janus 2 kinases.

Interleukin 5 (IL-5) induces proliferation and differentiation of B cells and eosinophils by interacting with its receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (beta c). Although both IL-5R alpha and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in tyrosine phosphorylation of molecules involved in IL-5 signal transduction, using an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or mutant IL-5R alpha together with intact beta c. The results revealed that the transfectants expressing truncated IL-5R alpha, which entirely lacks a cytoplasmic domain, together with beta c, showed neither protein-tyrosine phosphorylation nor proliferation in response to IL-5. This confirms that IL-5R alpha plays a critical role in protein-tyrosine phosphorylation which triggers cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of beta c and proteins containing Src homology 2 (SH2) and/or SH3 domains such as phosphatidyl-inositol-3 kinase, Shc, Vav, and HS1, suggesting their involvement in IL-5-mediated signal transduction. IL-5 stimulation significantly enhanced activities of Janus 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and Btk) and increased the tyrosine phosphorylation of JAK2 kinase. These results and recent data on signaling of growth factors taken together, multiple biochemical pathways driven by tyrosine kinases such as JAK2 and Btk are involved in IL-5 signal transduction.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase.

Bruton tyrosine kinase (Btk) has been implicated as the defective gene in both human and murine B-cell deficiencies. The identification of molecules that interact with Btk may shed light on critical processes in lymphocyte development. The N-terminal unique region of Btk contains a pleckstrin homology domain. This domain is found in a broad array of signaling molecules and implicated to function in protein-protein interactions. By using an in vitro binding assay and an in vivo competition assay, the pleckstrin homology domain of Btk was shown to interact with the beta gamma dimer of heterotrimeric guanine nucleotide-binding proteins (G proteins). A highly conserved tryptophan residue in subdomain 6 of the pleckstrin homology domain was shown to play a critical role in the binding. The interaction of Btk with beta gamma suggests the existence of a unique connection between cytoplasmic tyrosine kinases and G proteins in cellular signal transduction.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement.

We evaluated in WEHI 231 B cells the time-dependent responses of Lyn, Blk, Btk, Syk, and three members of the Jak family of protein tyrosine kinases following antibody-mediated surface engagement of the B-cell antigen receptor. Our results show that the enzyme activities of Lyn and Blk were stimulated within seconds of antigen receptor engagement and correlated with the initial tyrosine phosphorylation of the Ig alpha and Ig beta subunits of the B-cell antigen receptor. Btk enzyme activity was also transiently stimulated and was maximal at approximately 5 min after B-cell receptor surface binding. Syk activity gradually increased to a maximum at 10-30 min following receptor ligation and was found to parallel the association of Syk with the tyrosine phosphorylated Ig alpha and Ig beta subunits of the receptor. While the specific activities of the Jak1, Jak2, and Tyk2 protein tyrosine kinases were unaltered following B-cell receptor ligation, the abundance of Jak1 and Jak2 were increased 3- to 4-fold within 10 min of receptor engagement. These results demonstrate that multiple families of non-transmembrane protein tyrosine kinases are temporally regulated during the process of B-cell antigen receptor-initiated intracellular signal transduction.

Amino Acid Sequence↗
PubMed1994

Structural characterization of porcine enteropeptidase.

Enteropeptidase (EC 3.4.21.9) is a key enzyme in the intestinal digestion cascade responsible for the conversion of trypsinogen to trypsin, which then activates various pancreatic zymogens. In order to structurally characterize the enzyme, we purified the enzyme from porcine duodenal mucosa and showed that it consists of three polypeptide chains, which we named "mini" chain (M chain), light chain (L chain), and heavy chain (H chain) in order of increasing molecular size. Based on their NH2-terminal sequences, a cDNA clone for porcine enteropeptidase was isolated and analyzed. The clone was 3597 base pairs long, which encoded 1034 amino acid residues of a single-chain precursor form of enteropeptidase. The precursor contained an additional NH2-terminal 51-residue sequence including a putative internal signal sequence, followed by the M chain (66 residues), the H chain (682 residues), and the L chain (235 residues) in that order. The H chain had regions partially homologous in sequence with low density lipoprotein receptor and complement components. On the other hand, the L chain was highly homologous with the catalytic domains of trypsin-like serine proteinases. The structural model of the L chain suggests that the sequence, Arg885-Arg-Arg-Lys888, is probably involved in the unique substrate specificity of the enzyme, preferring acidic amino acid residues at the P2-P5 sites.

Amino Acid Sequence↗
PubMed1994

Glucocorticoids inhibit the proliferation of mucosal cells and enhance the expression of a gene for pepsinogen and other markers of differentiation in the stomach mucosa of the adult rat.

Adrenalectomy caused a significant decrease in the mucosal level of pepsinogen in the adult rat stomach. This decrease was mainly due to a reduction in the level of the main component of rat pepsinogen isozymogens, namely, Pg1 and in the level of expression of Pg1 mRNA, with a maximal effect being evident 48 hours after operation. Immunohistochemical analysis revealed that the level of expression of Pg1 in the pepsinogen-producing cells was decreased throughout the stomach mucosa and this decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increased the proliferation of mucosal cells and suppressed the expression of cathepsin E and class III mucin, markers of differentiated stomach mucosa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pg1 mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pg1 gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcription of Pg1 gene in fully differentiated stomach mucosa and that glucocorticoids are important regulators of both the function and the morphology of stomach mucosal cells.

Adrenalectomy↗
PubMed1994

Biological-clinical significance of selective loss of HLA-class-I allelic product expression in squamous-cell carcinoma of the uterine cervix.

To determine possible correlations between the selective loss of HLA-class-I allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-I heavy-chain expression associated with beta 2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 25 HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic product(s), but not with HLA-A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-I alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-I molecules may have different immune functions as restriction elements in T-cell-mediated cytotoxicity.

Adult↗
PubMed1994

Effect of omeprazole on secretion, synthesis and the gene expression of pepsinogen in the guinea pig stomach mucosa.

The effects of omeprazole, a proton pump inhibitor, on gene expression, protein synthesis, intracellular storage and secretion of pepsinogen in guinea pig stomach were investigated. After treatment with omeprazole for five days, acid and pepsinogen secretion into the gastric lumen was significantly reduced. Concomitant with this, there was an increase in intracellular pepsinogen as demonstrated by increased pepsin activity in the gastric mucosa, more intense immunohistochemical staining by antibodies specific for pepsinogen and accumulation of secretory granules in the cells producing pepsinogen. In these cells, the amount of pepsinogen mRNA was reduced as revealed by Northern blotting and in situ hybridization. Ultrastructurally the endoplasmic reticulum of these cells was poorly developed, the findings being consistent with a reduction in protein synthesis. It appears that omeprazole inhibits the secretion of pepsinogen, increasing the intracellular store and leading to the reduction in gene expression probably by a feedback mechanism and consequent reduction in pepsinogen synthesis. Since these changes were most evident in the acid-secreting fundic gland mucosa, as compared with other mucosae secreting only pepsinogen, namely pyloric and duodenal mucosa, it appears probable that these changes are linked with omeprazole-induced reduction in the acid secretion.

Animals↗
PubMed1994

Role of Bruton's tyrosine kinase in immunodeficiency.

The genetic defect associated with human X-linked agammaglobulinemia and murine X-linked immunodeficiency was recently shown to result from lack of function of a new cytoplasmic tyrosine kinase, called Bruton's tyrosine kinase (Btk). The phenotypes associated with these immunodeficiencies indicate that Btk plays a critical role in B-lymphocyte development. The distinctive protein structure of Btk and preliminary functional studies suggest that Btk may act in a novel manner in a variety of signaling pathways.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Craniofacial cleft with naso-ethmoidal encephalocele--case report.

The anterior skull base of a patient with a craniofacial cleft with naso-ethmoidal encephalocele was reconstructed using temporo-parietal and frontal galea-pericranial flaps and free cranial bone grafts, to prevent meningitis caused by trans-nasal infection. The patient had frequent episodes of meningitis before surgery, however, no episodes of meningitis have been observed up to 1 year postoperatively.

Bone Transplantation↗
PubMed1994

Cyclic regulation of B220 antigen expression in immature B cell lines.

Three independent immature B cell lines transformed with temperature-sensitive mutants of Abelson murine leukaemia virus (A-MuLV) persistently expressed B220 antigen detected by both of the anti-B220 antibodies RA3-6B2 and 14.8 during culture at the permissive temperature (35 degrees C). RA3-6B2 recognizes the B220 eptiope and that 14.8 is a CD45RA antibody. However, when the culture temperature was shifted up to the non-permissive temperature (39 degrees C) and the culture was continued for 2-3 weeks, a population of the cells (RA3-6B2-14.8+ cells) that lost RA3-6B2 antigen appeared in all three cell lines. From these populations, RA3-6B2-14.8+ subclones were independently isolated by limiting dilution and the phenotype was stable during culture at the permissive temperature. When the culture temperature of the RA3-6B2-14.8+ subclones was shifted up to the non-permissive temperature and the culture was continued for 2-3 weeks, RA3-6B2 antigen was re-expressed in a subpopulation of the RA3-6B2-14.8+ cells. These results demonstrated cyclic regulation of B220 antigen expression during proliferation and/or differentiation of immature B cell lines.

Animals↗
PubMed1994

Fetal rat glandular stomach epithelial cells differentiate into surface mucous cells which express cathepsin E in the absence of mesenchymal cells in primary culture.

It is well established that the differentiation of glandular stomach epithelial cells is affected by many factors including epithelial-mesenchymal interactions. To clarify the control mechanism of their differentiation, we developed a primary culture system for fetal rat glandular stomach epithelial cells, and examined their differentiation in the absence of mesenchyme. Pure glandular stomach epithelial tissues obtained from 16.5-day fetal rats proliferated rapidly, increasing their number about 20 times in the first 7 days. The epithelial nature of the cells was confirmed by the presence of cytokeratin in the cells. Glandular stomach epithelial cells formed simple cuboidal/squamous epithelia with many mucous granules in their cytoplasm, and exhibited epithelial polarity with microvilli on the luminal surface, basal lamina-like material on the basal surface, and junctional complexes in the apical region. Biochemical analysis showed that the cells expressed acid protease activity in culture. Previous studies showed that glandular stomach epithelial cells specifically expressed two types of acid proteases: pepsinogens in chief and mucous neck cells, and cathepsin E in surface mucous cells. Immunohistochemical studies using specific antibodies showed that the cultured cells expressed cathepsin E but not pepsinogens, and the result was confirmed by zymogram and Western blotting analysis. We thus concluded that fetal rat glandular stomach epithelial cells differentiated into surface mucous cells that expressed cathepsin E in primary culture in the absence of mesenchyme.

Animals↗
PubMed1994

The superficial temporal and retromandibular veins as guides to expose the facial nerve branches.

The superficial temporal vein and retromandibular vein were used as a guide to expose facial nerve branches in the parotid gland, and this procedure was applied to open reduction of mandibular condyle fractures (14 patients) and to superficial parotidectomy (6 patients). The advantages of this method are as follows: It is very easy to identify the superficial temporal vein as a guide, and it produces very little surgical stress because the procedure for exposing the facial nerve branches through the course of the vein is the same as the procedure for exposing the condyle and elevating the superficial lobe of the parotid gland.

Adolescent↗
PubMed1994

Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.

Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co-immunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

[Immunohistochemical study on the expression of carbohydrate antigens in normal squamous epithelia and squamous cell carcinomas of the uterine cervix].

The expression of 4 kinds of carbohydrate antigens, CA50, CA19-9, sialyl SSEA-1, and DU-PAN-2 was studied immunohistochemically in 15 normal cervical squamous epithelia and 49 cervical carcinomas. (1) In normal epithelia, CA50 and CA19-9 were expressed in all cell layers and all cell layers except for the basal layer, respectively, and a gradual decrease in the intensity of staining was observed in the upper layer. Sialyl SSEA-1 was expressed only in the superficial layer, but DU-PAN-2 was not found in any normal epithelia. (2) In cervical carcinomas, CA50, CA19-9, sialyl SSEA-1 and DU-PAN-2 were observed in 51.0%, 49.0%, 55.1% and 26.7%, respectively. (3) The number of Ki67 positive cells tended to be lower in the area with sialyl SSEA-1 immunostaining. (4) In the cases in which sialyl SSEA-1 positive cells were distributed diffusely in cancer nests, the incidence of lymph node metastasis was significantly higher. These result suggest that the expression of CA50, CA19-9 and sialyl SSEA-1 is related to the differentiation of normal squamous epithelial cells, and sialyl SSEA-1 may be related to cell differentiation also in cervical carcinomas, and the features of its expression may be useful in predicting the biologic properties of cervical carcinomas.

Adult↗