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Biomedical subjects

M Hibi

Publications and source records attributed to M Hibi.

At least 55 records · Page 3Linked to original sources

[Postoperative mediastinitis after the coronary artery bypass grafting using internal thoracic artery graft].

It has been pointed out in general that the resistance against infection is decreased in the diabetic patients. This problem is very important in patients undergoing major surgery. In cardiovascular surgery, the median wound infection may result in life threatening sequelae. We have used the internal thoracic artery as the appropriate graft for its excellent long-term patency. In this series of the diabetic patients who underwent coronary artery bypass grafting with bilateral internal thoracic artery grafts, the incidence of postoperative mediastinitis was significantly higher than other cases. Therefore the use of bilateral internal thoracic artery grafts should be avoided, if possible in the diabetic patients.

Aged↗

Valvulotomy of calcified aortic valves using the neodymium: yttrium-aluminum-garnet (Nd:YAG) laser.

The neodymium: yttrium-aluminum-garnet (Nd:YAG, wavelength; 1064 nm) laser knife was used for valvulotomy of severely calcified aortic valves in 12 patients. The fibrous layer enveloping the calcium deposits was peeled off the valvular annulus and the native valvular leaflet. The underlying calcium deposits were then resected. The average aortic cross-clamp time was 69 +/- 21 minutes. The cardiopulmonary bypass time averaged 118 +/- 32 minutes. All of the patients were discharged from the hospital without complications. Laser valvulotomy can be used to resect severely calcified aortic valves without mechanical crushing, reducing the risk of embolization.

Aged↗

[Preoperative autologous blood donation in coronary artery bypass grafting in elderly patients].

Allogeneic blood transfusion still carries risks of transfusion reaction and infection. We examined the effect of a preoperative autologous blood donation (800-1,200 g) by subcutaneous epoetin alpha injection on a series of patients undergoing elective coronary artery bypass grafting (CABG). CABG was being performed with increased frequency in elderly patients. We have performed CABG in 18 patients over 65 years of age (elderly group). These patients were compared with 20 patients under 64 years of age (younger group). Postoperative bleeding and allogeneic blood transfusion were significantly larger in quantity in the elderly group than the younger group (p < 0.05). The incidence of allogeneic blood usage was significantly higher in the elderly group than the younger group (p < 0.05). Therefore, a preoperative autologous blood donation in CABG was considered to be not so effective for saving allogeneic blood transfusion and preventing transfusion reaction or infection in elderly patients.

Aged↗

STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition.

The signal transducer and activator of transcription molecules (STATs) play key roles in cytokine-induced signal transduction. However, their role in cell growth has not been clear. In the present study, we show that STAT3 plays a key role in the G1 to S phase cell-cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D2, D3 and A, and cdc25A, and the concomitant downregulation of p21 and p27. Furthermore, unexpectedly, we found that gp130 could induce the expression of p21 when STAT3 activation was suppressed. Such contradictory signals regulating cell-cycle progression could be simultaneously delivered from distinct cytoplasmic regions of gp130. We propose an 'orchestrating model' for cytokine and growth factor action in which contradictory signals are orchestrated to produce a specific effect in a target cell.

Cell Line↗

A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner.

The formation of Spemann organizer is one of the most important steps in dorsoventral axis determination in vertebrate development. However, whether the organizer forms autonomously or is induced non-cell-autonomously is controversial. In this report we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically. The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation. Furthermore, dharma expressed in the YSL induced the organizer in a non-cell-autonomous manner. These results provided the first identification of a zygotic gene to be implicated in the formation of an organizer-inducing center.

Amino Acid Sequence↗

Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase.

Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved in Gab1-mediated ERK activation.

Adaptor Proteins, Signal Transducing↗

Signal transduction through cytokine receptors.

Receptors for interleukins, colony stimulating factors, and hormones have a homology in their extracellular regions, characterized by the conserved cysteine residues and the tryptophan-serine-x-tryptophan-serine motif, thus, they are classified to the type 1 cytokine receptor superfamily. Janus tyrosine kinase (JAKs) have been found to be involved in the signal transduction through type I cytokine receptors. JAKs associate with the membrane proximal region in the cytoplasmic domain having box1 and box2, which are conserved among the family, and upon the stimulation JAKs can be aggregated following the receptor dimerization and activated probably by transphosphorylation. JAKs then phosphorylate the receptor and various signal transducing molecules, including STATs (signal transducer and activator of transcriptions) and other SH2-containing adapter molecules. STATs were initially identified as transcription factors containing a SH2 domain and regulating interferons-inducible genes. STATs can be tyrosine phosphorylated by JAKs and form dimer (either hetero- or homo-dimers) to enter the nucleus, resulting in the expression of a set of genes. On the other hand, adapter molecules such as Shc, GRB2, and SHP-2 have been shown to link the cytokine receptors to Ras, followed by the activation of the Raf-MEK-MAP kinase pathway, leading to the activation of various transcription factors in the nucleus. These two signals are generated by different ways upon the stimulation of the receptors and they elicit a variety of biological functions in various cell types. In this review, we will discuss the mechanism by which cytokines activate JAKs, STATs, and a variety of adapter molecules. We further discuss the roles of each signal transduction pathways in the expression of biological activities of cytokines.

Animals↗

[Cardiac surgery by the safe and easy insertion method with the J-shaped left ventricular vent catheter].

We experienced the safe and easy insertion method with the J-shaped left ventricular vent catheter. The catheter tip (about 15 cm) was vended in the J shape with the inner stainless steel introducer. This J-shaped catheter was inserted into the left atrium through the right upper pulmonary vein. Then this catheter was held vertically and only the outer silicone catheter was pushed into the left ventricle. In this method the catheter tip is turned to the front in the left atrium and inserted easily into the left ventricle along the anterior wall of the left atrium through the anterior margin of the mitral valve orifice.

Adult↗

[Coronary artery bypass grafting under the excellent heart exposure provided by the use of the coronary artery exposing tape].

We have used the coronary artery exposing tape devised by Akio Matsuura in 93 patients undergoing coronary artery bypass grafting. We could perform graft anastomosis more easily and safely by the use of this tape than by the conventional simple compression method of the heart with the gauzes. The heart was lifted anteriorly with the rotation by the tape pulled to the left side or to the caudal side. The right coronary artery branches were exposed excellently by the simple traction of the tape to the caudal side. The circumflex coronary artery branches were well exposed by one tape pulled to the left side and another tape to the right side over the heart with the counterclockwise rotation of the heart. In these procedures no complication was encountered in association with the traction of this tape.

Adult↗

[The long-term anterior chest wound pain after the cardiac surgery].

We discussed on the long-term anterior chest wound pain after the cardiac surgery by using a questionnaire. The risk of the left anterior chest wound pain was high significantly in the cases using the left internal thoracic artery compared with other cases. Participation of the division of the left upper pericardium and the adjacent soft tissue was highly suggested as the cause of this pain.

Adolescent↗

[Coronary artery bypass grafting performed by the simple and convenient graft supporter].

We have experienced a simple, safe and convenient technique for supporting the arterial or saphenous vein graft in the coronary artery bypass grafting. This graft supporter is made of cotton cloth with a 50 percent polyester mix. The supporter is twenty centimeters long and two centimeters wide. This supporter provides the complete fixation of the graft without the holding by the co-operater. Therefore the supporter allows very easy, safe and accurate graft anastomosis with the native coronary artery or the ascendinbg aorta. No complication was encountered in association with this procedure in 127 operations.

Coronary Artery Bypass↗

[The long-term anterior chest median wound keloid after the cardiac surgery].

We discussed on the long-term anterior chest median wound keloid after the cardiac surgery by using a questionnaire. The risk of the anterior chest median wound keloid was high significantly in the cases using the bilateral internal thoracic artery compared with the cases using no internal thoracic artery. Participation of the decreased blood supply was highly suggested as the cause of this keloid formation.

Adolescent↗

Left ventricular free wall rupture following mitral valve replacement.

During a 10-year period, 110 patients underwent mitral valve replacement (MVR). We experienced three left ventricular ruptures among these patients. Two had a type I immediate rupture, and one had a type III delayed rupture. Two patients (type I, III) survived after repair of the rupture. It was possible to control bleeding by manual compression with oxidized cellulose, collagen mat and fibrin glue with or without external mattress sutures. Following the repair, an intra-aortic balloon pump and sedative agents were used in both patients. In the other patient with a type I early rupture, control of bleeding was attempted by external direct suture using Teflon felt. The bleeding was controlled by this repair and the use of a left ventricular assist device, but the patient died of a brain infarction 5 days after the operation. The manual compression technique using oxidized cellulose, collagen mat and fibrin glue may be useful for minor lacerations, and for reinforcing repairs. The intra-aortic balloon pump and continuous sedation are useful for unloading the ventricle and reducing the tension on repairs.

Aged↗

Overexpression of neurogenin induces ectopic expression of HuC in zebrafish.

Several basic helix-loop-helix (bHLH) transcription factors are known to be involved in vertebrate neurogenesis. To investigate their roles in zebrafish neurogenesis, we isolated cDNAs for homologues of neurogenin and Math(-1)/atonal. The transcription of neurogenin was first detectable in zebrafish nervous system at late gastrulation stage. The expression of zebrafish neurogenin precedes and overlaps that of HuC, one of the earliest neuronal precursor markers. Injection of neurogenin mRNA into early stage zebrafish embryos induced ectopic expression of HuC. These results suggest that neurogenin may participate in the generation of HuC-expressing cells, implying its role in neuronal determination in zebrafish.

Amino Acid Sequence↗

Dual control of neurite outgrowth by STAT3 and MAP kinase in PC12 cells stimulated with interleukin-6.

IL-6 induces differentiation of PC12 cells pretreated with nerve growth factor (NGF). We explored the signals required for neurite outgrowth of PC12 cells by using a series of mutants of a chimeric receptor consisting of the extracellular domain of the granulocyte-colony stimulating factor (G-CSF) receptor and the cytoplasmic domain of gp130, a signal-transducing subunit of the IL-6 receptor. The mutants incapable of activating the MAP kinase cascade failed to induce neurite outgrowth. Consistently, a MEK inhibitor, PD98059, inhibited neurite outgrowth, showing that activation of the MAP kinase cascade is essential for the differentiation of PC12 cells. In contrast, a mutation that abolished the ability to activate STAT3 did not inhibit, but rather stimulated neurite outgrowth. This mutant did not require NGF pretreatment for neurite outgrowth. Dominant-negative STAT3s mimicked NGF pretreatment, and NGF suppressed the IL-6-induced activation of STAT3, supporting the idea that STAT3 might regulate the differentiation of PC12 cells negatively. These results suggest that neurite outgrowth of PC12 cells is regulated by the balance of MAP kinase and STAT3 signal transduction pathways, and that STAT3 activity can be regulated negatively by NGF.

Animals↗

Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK.

Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6. Janus kinases (JAKs) are known to associate with certain cytokine receptors, e.g. gp130, the signal transducing subunit of IL-6 receptor, and the common beta chain of IL-3 receptor, which can be activated upon receptor dimerization in response to cytokines. Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using a yeast two-hybrid system we have identified the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs.

Antigens, CD↗

Involvement of a common 10-amino-acid segment in the cytoplasmic region of CD40 but different MAP kinases in different CD40-mediated responses.

CD40-mediated signals can induce cell aggregation, proliferation and rescue from apoptosis in WEHI231. To define which segment of cytoplasmic domain of CD40 and how signals are involved in those events, we generated mutant CD40 transfectants. We demonstrated the same 10 amino acid segment that could bind to tumor necrosis factor receptor associated factor-2 and -3 mediated all those responses. However, activation pattern of mitogen activated protein kinases was different. Immunoglobulin M-mediated apoptosis was inhibited by CD40-mediated signal that activated c-Jun aminoterminal kinase synergistically. While, CD40 stimulus through the 10 amino acid segment alone that induced cell aggregation and proliferation resulted in activation of extracellular signal-regulated protein kinase 2.

Amino Acid Sequence↗