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Biomedical subjects

S Tsukada

Publications and source records attributed to S Tsukada.

At least 55 records · Page 3Linked to original sources
PubMed1996

Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan.

Deficiencies of Bruton's tyrosine kinase (Btk) have been implicated in the pathogenesis of human X-linked agammaglobulinemia (XLA). The distinctive phenotype observed in B-cell deficiency indicates the crucial role of Btk in B-cell development. This report describes a nationwide study of Btk deficiency in Japan, covering 51 XLA patients (35 independent families). Along with the identification of mutations, the resulting protein products were characterized by an in vitro kinase assay and a Western blot analysis. Thirty-one of the families were found to have mutations in the coding region of Btk. Although mutations were not found in the cDNA of 4 families, the Btk transcripts of these patients were greatly reduced. The identification of several novel missense mutations, in combination with the result of other studies, clarified the presence of two (missense) mutation hot spots, one in the SH1 and the other in the PH domain. The absence of kinase activity seen in 32 of the families underscored the importance of Btk protein analysis as a diagnostic indicator of XLA. The protein analysis also clarified the different effects of missense mutations on kinase activity and protein stability.

Adolescent↗
PubMed1995

Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines.

Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, although the cytoplasmic region of gp130 does not contain any catalytic domain. In this study we show that in addition to Jak family tyrosine kinase, the stimulation of gp130 by IL-6 plus soluble IL-6 receptor alpha induced the activation of Btk and Tec tyrosine kinases, whereas IL-3 and granulocyte colony-stimulating factor activated Tec but not Btk in a pro-B cell line. Furthermore, both Btk and Tec kinases were associated with gp130 without the ligand stimulation. Because Btk is a critical tyrosine kinase for B lymphopoiesis and Tec is considered to be involved in hematopoiesis, the results suggest the involvement of gp130-Btk-Tec signal pathway in early lymphohematopoiesis.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

Binding affinities of highly repetitive DNA components for a nuclear scaffold protein from rat-ascites hepatoma cells.

Separate samples of a self-ligated tandem dimer of a highly repetitive DNA component (369-bp HindIII fragment) from rat-ascites hepatoma nuclei were digested with different restriction enzymes that cleave only once in the monomer. The resulting 369-bp sequence-permuted monomers showed anomalously slow gel electrophoretic mobility. Of them, the XmnI fragment had the slowest mobility. This suggests that bending of the helix axis is the strongest in this fragment. Our previous work has shown that such a repetitive bent DNA has selective affinities for two nuclear scaffold proteins from rat liver that have molecular weights of 123,000 and 130,000 Hibino et al. (1992) Biochem. Biophys. Res. Commun., 184, 853-858; Hibino et al. (1993) Biochim. Biophys. Acta, 1174, 162-170). In the present experiment, it has been found that the nuclear scaffold fraction from rat-ascites hepatoma cells does not contain these proteins, but does have a repetitive bent DNA-binding protein that has a molecular weight of about 230,000. These results imply that there is some difference in the structure of nuclear DNA attachment region between rat liver and the hepatoma.

Animals↗
PubMed1995

Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain.

Bruton's tyrosine kinase (BTK) is a nonreceptor tyrosine kinase critical for B cell development and function. Mutations in BTK result in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Using a random mutagenesis scheme, we isolated a gain-of-function mutant called BTK* whose expression drives growth of NIH 3T3 cells in soft agar. BTK* results from a single point mutation in the pleckstrin homology (PH) domain, where a Glu is replaced by Lys at residue 41. BTK* shows an increase in phosphorylation on tyrosine residues and an increase in membrane targeting. Transforming activity requires kinase activity, a putative autophosphorylation site, and a functional PH domain. Mutation of the SH2 or SH3 domains did not affect the activity of BTK*. Expression of BTK* could also relieve IL-5 dependence of a B lineage cell line. These results show that transformation activation and regulation of BTK are critically dependent on the PH domain.

3T3 Cells↗
PubMed1995

Repair of complete syndactyly by tissue expansion and composite grafts.

Repair of complete syndactyly by a combination of tissue expansion and composite grafts from the glabrous non-weight bearing areas of the foot has been performed on three syndactylies in two patients. The commissure and the lateral areas of the proximal and middle phalanges were covered with expanded skin and the separated fingertips were covered with composite grafts. Without using an ordinary skin graft, this method can provide aesthetically excellent results with good skin colour and texture.

Female↗
PubMed1995

An easy method of vascular anastomosis for replantation of fingertips.

Many cases of successful replantation of fingertips have been reported; however, it still remains difficult for an inexperienced surgeon to anastomose very small vessels (especially veins of the fingertip) because their walls and lumina cannot be clearly defined. The authors report a simple method which is useful for anastomosis of small vessels. A colored silicone background is cut into a small, thread-like segment, and both ends are tapered. This segment is then introduced into the vessel lumen to serve as a vascular stent. The silicone vascular stent makes it easy to identify the vessel lumen and then to suture the vessel edges. It also prevents a through-stitch, the most common cause of anastomosis failure with small vessels. The silicone vascular stent is removed before the last suture is tied. This technique has been used for suturing small veins in the finger pulp or small arteries in zone I, and it will be most helpful for the inexperienced microsurgeon.

Amputation, Traumatic↗
PubMed1995

The use of a free medialis pedis flap for resurfacing skin defects of the hand and digits: results in five cases.

A free medialis pedis flap was used to repair skin defects of the fingers and hand in five patients, the flap sizes ranging from 2 x 3 cm to 5 x 10 cm. Four flaps survived completely, but the largest flap turned necrotic along the dorsal margin, which is thought to have resulted from an incorrect flap alignment. A free medialis pedis flap possesses several advantages: (1) It is very thin in comparison with other standard free flaps; (2) it can be used for small repairs, unlike many conventional free flaps; (3) it possesses two draining venous pathways, the vena comitans and the subcutaneous veins; (4) the diameters of its vessels are similar to those of the fingers; (5) it provides a good color and texture match for finger repairs; and (6) a good recovery of protective sensation is achievable, probably due to its thinness. However, this flap also has some disadvantages: A skin graft is usually required for donor-site closure, and it cannot be used as a sensory flap.

Adult↗