Contact dermatitis due to flurbiprofen.
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Adult↗
Biomedical subjects
T Tezuka
Publications and source records attributed to T Tezuka.
Fixed drug eruption induced by tosufloxacin tosilate.
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Aged↗
Analysis of serum lactate dehydrogenase and its isozymes during administration of granulocyte colony-stimulating factor in children.
Serum lactate dehydrogenase (LDH) activity is known to become elevated following granulocyte colony-stimulating factor (G-CSF) therapy in some patients, but no extensive studies on this phenomenon have been performed. In 26 children with malignancies in complete remission who received recombinant human G-CSF intravenously after combined chemotherapy, we measured serum LDH and its isozymes (81 episodes) before chemotherapy (pre-Tx), during administration of G-CSF (mid-Tx), and after stopping G-CSF (post-Tx) and compared the obtained data using paired t test. Twelve episodes were excluded from analysis because of liver dysfunction (alanine aminotransferase > 45 IU/L). Serum LDH at mid-Tx (343.1+/-19.8 IU/L; mean +/- SE) was significantly higher than that at pre-Tx (186.9+/-6.7 IU/L) and post-Tx, but this difference was observed only when change in white blood cell counts (WBCs) (WBC at mid-Tx minus WBC at pre-Tx) was greater than or equal to 4000/microL (58 episodes). Percentages of LDH isozymes 3, 4, and 5 at mid-Tx (23.5+/-1.0, 11.7+/-0.8, and 8.3+/-0.7) were significantly increased compared with those at pre-Tx (19.5+/-0.7, 6.3+/-0.3, and 4.2+/-0.5) and post-Tx, resulting in a significant decrease in percentages of LDH isozymes 1 and 2 at mid-Tx. In episodes of change in WBCs > or =4000/microL, change in LDH significantly correlated to changes in WBCs and granulocytes but not to change in lymphocytes or monocytes. These results suggest that serum LDH is significantly elevated during G-CSF administration in accordance with the increase in peripheral granulocytes, which accompanies change in the pattern of percentages of LDH isozymes.
Adolescent↗
Molecular cloning and characterization of a novel cbl-family gene, cbl-c.
We have cloned a novel gene, cbl-c, of mammalian cbl-family. The cbl-c gene is predicted to encode a protein of 52 kDa that has a phosphotyrosine-binding domain, a RING finger and a proline-rich region. Cbl-c shows 50% homology to the amino-terminal sequences of Cbl and Cbl-b, but a sequence corresponding to the carboxy-terminal half of Cbl and Cbl-b is largely missing in Cbl-c. The expression of cbl-c mRNA is distinct from that of cbl and cbl-b mRNAs, being high in the colon and small intestine, but undetectable in brain and lymphoid tissues. The cbl-c gene is mapped in 19q13.2-13.3. Finally, the 52 kDa Cbl-c protein binds to the EGF receptor and Fyn tyrosine kinase. We conclude that Cbl-c is a novel Cbl-family adaptor protein that would regulate intracellular signaling mediated by various tyrosine kinases.
Amino Acid Sequence↗
Cloning and characterization of Dfak56, a homolog of focal adhesion kinase, in Drosophila melanogaster.
The focal adhesion kinase (FAK) protein-tyrosine kinase plays important roles in cell adhesion in vertebrates. Using polymerase chain reaction-based cloning strategy, we cloned a Drosophila gene that is homologous to the vertebrate FAK family of protein-tyrosine kinases. We designated this gene Dfak56 and characterized its gene product. The overall protein structure and deduced amino acid sequence of Dfak56 show significant similarity to those of FAK and PYK2. Dfak56 has in vitro autophosphorylation activity at tyrosine residues. Expression of the Dfak56 mRNA and the protein was observed in the central nervous system and the muscle-epidermis attachment site in the embryo, where Drosophila position-specific integrins are localized. The results suggest that like FAK in vertebrates, Dfak56 functions downstream of integrins. Dfak56 was tyrosine-phosphorylated upon integrin-dependent attachment of the cell to the extracellular matrix. We conclude that the Dfak56 tyrosine kinase is involved in integrin-mediated cell adhesion signaling and thus is a functional homolog of vertebrate FAK.
Amino Acid Sequence↗
Identification of a novel Sry-related gene and its germ cell-specific expression.
Sox family proteins are characterized by a unique DNA-binding domain, a HMG box which shows at least 50% sequence similarity with mouse Sry, the sex-determining factor. At present almost 30 Sox genes have been identified. Members of this family have been shown to be conserved during evolution and to play key roles during animal development. Some are involved in human diseases, including sex reversal. Here we report the isolation of a novel member of the Sox gene family, Sox30, which may constitute a distinct subgroup of this family. Using a bacterially expressed DNA-binding domain of Sox30, we show that it is able to specifically recognize the ACAAT motif. Furthermore, Sox30 is capable of activating transcription from a synthetic promoter containing the ACAAT motif. The specific expression of Sox30 in normal testes, but not in maturing germ cell-deficient testes, suggests the involvement of Sox30 in differentiation of male germ cells. Mapping analyses revealed that the Sox30 gene is located on human chromosome 5 (5q33) and on mouse chromosome 11.
Animals↗
Application of a recombinant Fab fragment from a phage display library for sensitive detection of a target antigen by an inhibition ELISA system.
We have found that the recombinant Fab (rFab) produced by phage display system was detectable for a target antigen more sensitive than the parental monoclonal antibody (MoAb). The Fab phage display library was constructed from hybridoma cells producing APU-6 MoAb specific for a modified nucleoside, pseudouridine that have been studied as a urinary marker for malignancy. Fab-displayed phage clones were screened by a direct ELISA, and the single positive clone was finally obtained. Although the reaction pattern of rFab against pseudouridine and uridine was almost identical to that of MoAb, detection sensitivity of rFab was approximately 30 times higher than that of MoAb. Since the sensitivity of rFab was almost identical to that of Fab fragment prepared by papain digestion of MoAb, the increased sensitivity is considered to be the nature of Fab fragment. The sensitivity of established assay system was sufficient for quantitative determination of serum pseudouridine levels in healthy individuals and cancer patients. This procedure may be applicable for improvement of detection sensitivity of a MoAb-based inhibition ELISA system for drugs or low molecular weight compounds.
Amino Acid Sequence↗
PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A.
Fyn, a member of the Src-family protein-tyrosine kinase (PTK), is implicated in learning and memory that involves N-methyl-D-aspartate (NMDA) receptor function. In this study, we examined how Fyn participates in synaptic plasticity by analyzing the physical and functional interaction between Fyn and NMDA receptors. Results showed that tyrosine phosphorylation of NR2A, one of the NMDA receptor subunits, was reduced in fyn-mutant mice. NR2A was tyrosine-phosphorylated in 293T cells when coexpressed with Fyn. Therefore, NR2A would be a substrate for Fyn in vivo. Results also showed that PSD-95, which directly binds to and coclusters with NMDA receptors, promotes Fyn-mediated tyrosine phosphorylation of NR2A. Different regions of PSD-95 associated with NR2A and Fyn, respectively, and so PSD-95 could mediate complex formation of Fyn with NR2A. PSD-95 also associated with other Src-family PTKs, Src, Yes, and Lyn. These results suggest that PSD-95 is critical for regulation of NMDA receptor activity by Fyn and other Src-family PTKs, serving as a molecular scaffold for anchoring these PTKs to NR2A.
Animals↗
Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin alpha conjugate of skin.
The inhibitory properties of phosphorylated cystatin alpha (P-cystatin alpha) and a conjugated protein of the P-cystatin alpha with filaggrin linker segment peptide (FLSP) against the growth of Staphylococcus bacteria and poliovirus were investigated. Both the P-cystatin alpha and the conjugated protein (P-cystatin alpha-FLSP conjugate) as a model for the cornified envelope of skin inhibited the cysteine protease activity of Staphylococcus aureus V8. The protease activity was inhibited by normal cornified envelope of newborn rat skin, which contains P-cystatin alpha, and P-cystatin alpha in cornified envelope of newborn rat skin also suppressed the growth of S. aureus V8. When P-cystatin alpha or P-cystatin alpha-FLSP conjugate was added to cultured HeLa cells infected with poliovirus, 50-70% of the cell-death due to poliovirus infection was prevented. The poliovirus 3C protease activity in the infected HeLa cells was inhibited by P-cystatin alpha or P-cystatin alpha-FLSP conjugate. As a result, the processing of viral capsid peptides was suppressed. These findings suggest that P-cystatin alpha and P-cystatin alpha-FLSP conjugate could play the role of the barrier against microorganism infections due to inhibition of their cysteine protease activities.
Amino Acid Sequence↗
The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells.
We previously reported a novel monoclonal antibody KOR-SA3544 which predominantly reacted with a surface antigen (sSA3544) expressed on Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL). In the present study, we demonstrate that the antibody specifically recognized nonspecific cross-reacting antigen (NCA)-50/90 (CD66c), one of the carcinoembryonic antigen (CEA)-related glycoproteins encoded by a member of the CEA gene family. In addition, we show that the SA3544 antigen (NCA-50/90) was invariably expressed in cytoplasm of all of the human leukemic cell lines examined (sSA3544-positive B-lymphoid two, sSA3544-negative T or B-lymphoid and non-lymphoid 24) regardless of the presence or absence of surface expression of this antigen. Immunoelectromicroscopic examination revealed that the cytoplasmic antigen was mainly present in granules in sSA3544-positive leukemia cells, whereas it was diffusely present in cytosol in sSA3544-negative leukemia cells. Thus, among members of the CEA family, NCA-50/90 was first demonstrated to be expressed not only on the surface of some leukemia cells, but also in cytoplasm of various types of leukemia cells.
Antibodies, Monoclonal↗
p16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation.
The p16 gene encoding a specific inhibitor of cyclin-dependent kinases 4 and 6 has been reported to be inactivated at a variety of rates in malignant tumors. We studied frequency and mechanism of inactivation of the p16 gene in various types of childhood acute lymphoblastic leukemia (ALL) using 36 leukemic cell lines established from children (B precursor-ALL, 28; B-ALL/Burkitt's lymphoma, 3; and T-ALL, 5). On Southern blot, homozygous deletions or hemizygous deletions with rearrangement were detected in 14 cell lines. The expression of p16 protein was not observed on Western blot in 18 of 22 cell lines with intact p16 gene, but induced in 16 cell lines after treatment with the demethylating agent, indicating the silencing of the p16 gene by hypermethylation. Of note, the p16 gene was inactivated by hypermethylation of the 5' CpG island in nine of nine cell lines with 11q23 translocation, but was restored with the treatment of the demethylating agent. Partial methylation of the p16 gene was also demonstrated in three of eight primary leukemia samples with this translocation, suggesting that the p16 gene inactivation by hypermethylation might play a role in the leukemogenesis and disease progression of ALL with 11q23 translocation.
Blotting, Southern↗
An immunohistochemical study of abnormal keratinocyte differentiation in molluscum contagiosum.
To investigate abnormalities in the keratinization process in lesional epidermis of molluscum contagiosum, production of filaggrin, loricrin, Ted-H-1 antigen, involucrin, cystatin A and CD95 ligand (CD95L) was investigated using specific antibodies. Anti-filaggrin monoclonal antibody (MoAb) did not react with keratohyalin granules (KHG), but with the substance around virus particles in the stratum corneum. KHG reacted with anti-loricrin polyclonal antibody (PoAb) and anti-Ted-H-1 MoAb. Anti-involucrin PoAb and anti-cystatin A PoAb reacted with materials in the cytoplasm of the middle stratum spinosum to the stratum granulosum. CD95L was expressed in the cell membrane region of the living cell layers in lesional epidermis. These observations suggest that the keratinization process may be altered in molluscum contagiosum.
Biomarkers↗
Bikunin, a serine protease inhibitor, is present on the cell boundary of epidermis.
Bikunin, which is an inhibitor of serine proteases, is widely distributed in human tissues, including liver, kidney, and mucous membranes of the stomach and colon. The aim of this study was to clarify whether bikunin is expressed in human epidermis and its appendages. Immunoblot analysis using a specific polyclonal antibody to bikunin revealed that a single 43 kDa protein is present in the cell lysate from the human keratinocyte cell line HaCaT. Immunohistochemically, dotted reaction products stained with anti-bikunin antibody were localized on the cell boundary in both basal and spinous cell layers, except on the cell boundary of the basal cells facing the basal membrane. There were no reaction products in the granular-horny cell layers. Reaction products stained with anti-bikunin antibody were also observed on the hair bulb cells and eccrine sweat gland cells, but not on apocrine sweat glands. Also, reaction products were observed on the luminal surface of the renal proximal tubules and in the cytoplasm of these cells. In immunoelectron microscopy, gold particles were observed on the cell membranes close to the desmosomal structures. Reverse transcription-polymerase chain reaction and northern blot analyses showed that mRNA specific for bikunin was expressed in HaCaT cells and human epidermal keratinocytes obtained from suction blisters, and was contained in a commercially available human keratinocyte cDNA preparation. These findings indicate that bikunin is expressed in keratinocytes and may play an important part in regulating keratinocytes in either mitosis or inflammation.
Antibodies↗
Use of Tc-99m DTPA galactosyl human serum albumin to predict postoperative residual liver function.
PURPOSE: Residual liver uptake at 15 minutes (RLU15), a new index for predicting residual liver function after excision of hepatocellular carcinoma, was evaluated using dynamic liver images and SPECT by Tc-99m DTPA galactosyl human serum albumin. MATERIALS AND METHODS: In 13 cases of hepatectomy, RLU15 was compared with postoperative serum prothrombin levels, serum bilirubin levels, and ascites. RESULTS: RLU15 showed good correlation with both the prothrombin activity and the serum bilirubin, with correlation coefficients of r = 0.829 and r = -0.757. CONCLUSION: This new index appears useful for predicting residual liver function after hepatectomy.
Ascites↗
Drug eruption due to tribenoside.
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Administration, Oral↗
Overexpression of CD11b on eosinophils in atopic dermatitis: downregulation by cyclosporin A and upregulation by interleukin 5.
We examined the level of expression of CD11b on eosinophils in pripheral blood samples from patients with atopic dermatitis (AD) and non-AD volunteers. Eosinophils were defined using a new method employing CD14/CD45 and a backgate technique. Overexpression of CD11b was noted in eosinophils of AD patients. Treatment of AD with cyclosporin A resulted in clinical improvement as well as reduction in the expression of CD11b. Stimulation of eosinophils from patients with inactive AD by interleukin 5 upregulated the expression of CD11b on these cells. Our results suggest that the expression of CD11b surface molecule on eosinophils may play an important role in the activity of AD.
Cyclosporine↗
[Local complications of the intestinal tract in patients with ulcerative colitis].
Various types of local complication of the intestinal tract are recognized in patients with ulcerative colitis. Among those local complications, massive bleeding, perforation and toxic megacolon require emergent operation in order to avoid fetal condition. Stricture of the colon, fustura formation and intra-abdominal abscess are rare complication in patients with ulcerative colitis, but sometimes require surgical treatment. Colitic cancer is another serious complication which develops highly advanced stage. Surveillance of the colon by endoscopy is necessary to obtain early diagnosis of the colitic cancer.
Colitis, Ulcerative↗
Surgical treatment of Cronkhite-Canada syndrome associated with protein-losing enteropathy: report of a case.
PURPOSE: The case of a patient with Cronkhite-Canada syndrome, who developed a protein-losing enteropathy, is reported. METHODS: After localization of the protein-losing region, a right colectomy was performed. RESULTS: Hypoproteinemia and ectodermal changes improved postoperatively. CONCLUSIONS: Surgery is an effective treatment for protein-losing enteropathy in Cronkhite-Canada syndrome. Ectodermal changes improve after correcting malnutrition.
Female↗