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Satoshi Takagi

Publications and source records attributed to Satoshi Takagi.

35 records · Page 2Linked to original sources
PubMed2003

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities.

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated form (HBdeltatm) of the molecule. HB(uc/uc) mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBdeltatm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control.

Animals↗
PubMed2003

T cell-specific disruption of arylhydrocarbon receptor nuclear translocator (Arnt) gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution.

The arylhydrocarbon receptor nuclear translocator (ARNT) is a member of the basic helix-loop-helix, PER-ARNT-SIM family of heterodimeric transcription factors, and serves as a dimerization partner for arylhydrocarbon receptor (AHR) and hypoxia-inducible factor-1alpha. To assess the function of ARNT in T cells, we disrupted the Arnt gene specifically in T cells of mice by conditional gene targeting using T cell-specific p56(lck)-Cre (Lck-Cre) transgenic Arnt-floxed mice. Thus generated, T cell-specific Arnt-disrupted mice (Lck-Cre;Arnt(flox/Delta) transgenic mice) exhibited complete loss of the expression of ARNT protein only in T cells, and were viable and appeared normal. The Arnt-disrupted T cells in the thymus were phenotypically and histologically normal. The Arnt-deficient T cells in the spleen were capable of responding to TCR stimulation in vitro. However, unlike normal mice in which exposure to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AHR ligand, resulted in thymic involution, the thymus of Lck-Cre;Arnt(flox/Delta) mice were resistant to TCDD treatment in vivo. In contrast, benzo(a)pyrene, another AHR ligand, still caused thymic involution in Lck-Cre;Arnt(flox/Delta) mice. Finally, fetal thymus organ culture using Lck-Cre;Arnt(flox/Delta) and K5-Cre;Arnt(flox/Delta) (epithelial cell-specific Arnt-disrupted mice) showed that thymocytes rather than thymic epithelial cells are predominantly responsible for TCDD-induced thymic atrophy. Our results indicate that ARNT in T lineage cells is essential for TCDD-mediated thymic involution.

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PubMed2003

Rat model of laryngeal transplantation with normal circulation maintained by combination with the tongue.

Recent research on laryngeal transplantation used a rat model with physiologically abnormal circulation, because the common carotid artery was used for venous drainage. Since a model with normal circulation is better for accurate assessment, we developed a vascularized laryngeal graft, using the common carotid artery as the arterial supply and the external jugular vein as the venous drainage. The transplant included other tributaries from the tongue and the pharynx by combination with the tongue, because the tributaries from the larynx were very small. Ten transplants were performed. The transplanted organs were examined daily. Seven days after transplantation, the composite grafts were evaluated histologically. The mortality rate was 10%. All composite grafts were fully viable, and their structure was maintained in the remaining nine rats. Our model is appropriate for experiments on laryngeal transplantation.

Animals↗
PubMed2003

Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function.

Aryl hydrocarbon receptor nuclear translocator (ARNT), a transcription factor of the Per/AHR/ARNT/Sim family, regulates gene expression in response to environmental stimuli including xenobiotics and hypoxia. To examine its role in the epidermis, the Cre-loxP system was used to disrupt the Arnt gene in a keratinocyte-specific manner. Gene-targeted, newborn mice with almost normal appearance died neonatally of severe dehydration caused by water loss. Histology showed small changes in the architecture of cornified layers, with apparently preserved intercorneocyte lamellar structures responsible for the skin barrier function. In contrast, HPLC/ion-trap mass spectrometry revealed significant alterations in the compositions of ceramides, the major components of the lamellae. The murine epidermal ceramides normally contain 4-sphingenine and 4-hydroxysphinganine. In Arnt-null epidermis, 4-sphingenine was largely replaced by sphinganine and the amounts of ceramides with 4-hydroxysphinganine were greatly decreased, suggesting deficiency of dihydroceramide desaturases that catalyze the formation of both 4-sphingenyl and 4-hydroxysphinganyl moieties. A desaturase isoenzyme, DES-1, prefers desaturation, but DES-2 catalyzes both reactions to a similar extent. Transcript levels of Des-2, but not Des-1, were considerably decreased in cultured keratinocytes from Arnt-null epidermis. These results indicate that proper ceramide compositions through 4-desaturation regulated by ARNT are crucial for maintaining the epidermal barrier function.

Animals↗
PubMed2002

STAT3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of p130(cas).

We previously reported that STAT3 plays a crucial role in transducing a signal for migration of keratinocytes (Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., and Takeda, J. (1999) EMBO J. 18, 4657-4668). To clarify the role of STAT3 in signaling the migration, we studied the intracellular signaling pathway through an integrin receptor in STAT3-deficient keratinocytes. STAT3-deficient keratinocytes demonstrated increased adhesiveness and fast spreading on a collagen matrix. Staining with anti-phosphotyrosine antibody revealed that STAT3-deficient keratinocytes had an increased number of tyrosyl-hyperphosphorylated focal adhesions. Analyses with immunoprecipitation revealed that p130(cas) was constitutively hyperphosphorylated on tyrosine residues, while other focal adhesion molecules such as focal adhesion kinase and paxillin were not. Transfection of STAT3-deficient keratinocytes with an adenoviral vector encoding the wild-type Stat3 gene reversed not only impaired migration but also the increased tyrosine phosphorylation of p130(cas). These results strongly suggest that STAT3 in keratinocytes plays a critical role in turnover of tyrosine phosphorylation of p130(cas), modulating cell adhesiveness to the substratum leading to growth factor-dependent cell migration.

Animals↗
PubMed2002

Internal jugular vein occlusion in head and neck microsurgical reconstruction.

The internal jugular vein has been the preferred recipient vein in head and neck microsurgical reconstruction. However, recent reports have demonstrated internal jugular vein occlusion after functional neck dissection. The purpose of this article is to demonstrate and discuss the possibility of recipient internal jugular vein occlusion after free tissue transfer. Of 58 patients who received an end-to-side venous anastomosis with the internal jugular vein, four cases of recipient internal jugular vein occlusion were detected during the early postoperative period. Although the success rate of end-to-side anastomosis with the internal jugular vein may be high, microsurgeons should be aware of the possibility of internal jugular vein occlusion.

Aged↗
PubMed2002

Breast reconstruction using the sensate latissimus dorsi musculocutaneous flap.

The authors performed immediate breast reconstruction on four patients using a sensate latissimus dorsi musculocutaneous flap accompanied by neurorrhaphy during the past 6 years. In the neurorrhaphy, the lateral cutaneous branch of the dorsal primary divisions of the seventh thoracic nerve, which controls the sensation of the myocutaneous flap, was anastomosed to the lateral cutaneous branch of the fourth intercostal nerve, which controls the sensation of the breast. The subjects consisted of four patients whose postoperative follow-up period was 14 to 29 months, with an average of 19.3 months. The control subjects consisted of 10 cases with a latissimus dorsi musculocutaneous flap whose sensory nerve had not been reconstructed (postoperative follow-up period, 15 to 49 months; average, 26.9 months). The sensory examination included tests of touch, pain, and temperature. The innervated musculocutaneous flap sensation showed gradual recovery at about 6 months after surgery and reached the value of the normal side after about 1 year. In the control subjects, the recovery was gradual after more than 1 year and reached the value of the normal side in only some of the control subjects. On the basis of these findings, the authors consider the present technique to be useful for the recovery of sensation in immediate breast reconstruction.

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PubMedDate not supplied

Relationship of disease progression and plasma histamine concentrations in 11 dogs with mast cell tumors.

Plasma histamine concentrations (PHCs) were measured serially over 9 months or until death in 11 dogs with mast cell tumors (MCTs). Eight dogs had grossly visible disease and the other 3 dogs had microscopic disease. Initial PHCs in the dogs with gross disease were significantly higher than PHCs in healthy dogs (median, 0.73 ng/mL and 0.19 ng/mL respectively; P < .009), whereas initial PHCs in dogs with microscopic disease showed no difference from controls. Seven dogs subsequently had progressive increases in PHC, and developed hyperhistaminemia (median, 14.0 ng/mL; range, 5.11-30.1 ng/nL). These 7 dogs died from MCTs, and 1 had general weakness with rapid lysis of a large tumor burden after radiation therapy. PHCs of the other 4 dogs were less than 1 ng/mL during the study. These 4 dogs were still alive with adequate control of the tumor at the conclusion of the study. Four of the 11 dogs initially had gastrointestinal (G1) signs, which abated soon after administration of histamine-2 (H-2) blockers. No significant difference was found between PHCs in dogs with GI signs and those without GI signs (median, 0.86 ng/mL and 0.35 ng/mL. respectively). Thereafter, 7 dogs had serious GI complications for which H-2 blocker therapy was ineffective. PHCs in these 7 dogs were extremely high (median, 12.2 ng/mL; range, 3.42-30.1 ng/nL). Results of this study demonsrated that PHC was one factor related to disease progression, and indicated that marked hyperhistaminemia was associated with the GI signs refractory to H-2 blocker therapy in dogs with MCTs.

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PubMedDate not supplied

Successful treatment for combined pancreatoduodenal injury by a second-stage pancreatojejunostomy following pancreatoduodenectomy.

A case of combined pancreatoduodenal injury requiring pancreatoduodenectomy is described. A two-stage approach was used, which included a pancreatoduodenectomy followed by a tube pancreatostomy for complete external drainage of pancreatic juice and subsequent second-stage pancreatojejunostomy. This approach, first advocated by Miyagawa et al., enabled us to handle the normal soft pancreas without any complications. It is suggested that the described second-stage pancreatojejunostomy can be considered as an alternative method of restoring pancreatoenteric continuity following pancreatoduodenectomy in emergency cases.

Abdominal Injuries↗
PubMedDate not supplied

Results of 404 hepatic resections including 80 repeat hepatectomies for hepatocellular carcinoma.

BACKGROUND/AIMS: To evaluate our treatment protocol applied to patients with hepatocellular carcinoma. The protocol consists of the selection criteria for hepatectomy, the use of techniques that minimize intraoperative blood loss, strict follow-up after surgery, and an aggressive surgical approach for intrahepatic recurrence. METHODOLOGY: We conducted a retrospective cohort study that included 337 patients with hepatocellular carcinoma treated between 1990 and 2001. The type of resection was selected according to the serum bilirubin value and the indocyanine green retention rate at 15 minutes. Perioperative data and long-term outcome were examined. RESULTS: We performed 324 initial hepatectomies with an in-hospital mortality rate close to zero. There was one operative death and one hospital death (0.3% each), and the 5-year survival rate for all patients was 53.2%. Eighty repeat liver resections, including 18 third and two fourth, were performed with no mortality, and the 5-year survival rate was 52.9% after the second hepatic resection. The resectability rate for second and third hepatectomies reached 29% and 33% of all patients with isolated liver recurrence, respectively. CONCLUSIONS: Liver resection is a safe and effective treatment modality for hepatocellular carcinoma. Our results are likely attributable to the routine application of our treatment protocol.

Adult↗