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Hiroaki Konishi

Publications and source records attributed to Hiroaki Konishi.

18 recordsLinked to original sources
PubMed2006

CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP.

To decipher the global network of the epidermal growth factor (EGF) receptor-mediated signaling pathway, a large scale proteomic analysis of tyrosine-phosphorylated proteins was conducted. Here, we focus on characterizing a novel protein, CFBP (CIN85/CD2AP family binding protein), identified in the study. CFBP was found to be phosphorylated at tyrosine 204 upon EGF stimulation, and the CIN85/CD2AP family was identified as a binding partner. A proline-rich motif of CFBP is recognized by one of the three Src-homology 3 domains of CIN85/CD2AP, and the affinity of the interaction is regulated by the tyrosine phosphorylation of CFBP. They co-localize in actinenriched structures, and overexpression of CFBP induced morphological changes with actin reorganization. Furthermore, CFBP accelerated the EGF receptor's down-regulation by facilitating the recruitment of Cbl to the CD2AP/CIN85 complex. Two spliced variants of CFBP lacking either exon 5 or 8 are also expressed, and the variant lacking exon 5 without the proline-rich motif lacks the ability to bind to the CIN85/CD2AP family. The CFBP protein seems to play a key role in the ligand-mediated internalization and down-regulation of the EGF receptor.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Suppression of the ligand-mediated down-regulation of epidermal growth factor receptor by Ymer, a novel tyrosine-phosphorylated and ubiquitinated protein.

The ligand-mediated down-regulation of the growth factor receptors is preceded by the involvement of various other factors. In particular, a ubiquitin ligase, Cbl, plays a central role in this event. Several candidates that have potential effects on the negative control of the epidermal growth factor (EGF) receptor have now been identified by our recent studies in phospho-proteomics. Among these molecules, we focus on characterizing a novel protein, Ymer, which is a tyrosine-phosphorylated and ubiquitinated protein. Ymer is found to be phosphorylated at tyrosine 145 and 146 upon EGF stimulation, and lysine 129 of Ymer has been identified as a ubiquitination site. Ymer has two motifs interacting with the ubiquitin (MIU) domains that might function as a binding site for the ubiquitinated EGF receptor. Although Ymer and EGF receptors are associated in an EGF-dependent manner, their interaction is required not only for MIU domains but also for the tyrosine phosphorylation of Ymer. Phosphorylated Ymer is mainly located at the plasma membrane with EGF receptor and functions in its endocytosis and degradation. Furthermore, EGF-mediated secondary modifications of an activated-EGF receptor are inhibited by overexpressing Ymer in COS7 cells. Therefore, Ymer may have competitive effects on the activation of the EGF receptor. Our findings suggest that Ymer functions as a novel inhibitor for the down-regulation of the EGF receptor and plays a crucial role for regulating the amount of the EGF receptor on the cell surface membrane.

Cell Line↗
PubMed2006

Mutation of the PI3' kinase gene in a human colon carcinoma cell line, HCC2998.

HCC2998 is a highly differentiated human colon carcinoma cell line, which has been shown to be converted to a poorly differentiated one after expression of a constitutively active phosphatidylinositol 3-kinase (PI3' kinase). These cells express aberrant sizes of a regulatory subunit of PI3' kinase, p85alpha, with molecular weights of 50 and 76 kDa at a very low level. To elucidate how these cells express these proteins, we analyzed mutations within the p85alpha gene. DNA sequencing analysis revealed that these mutant proteins were generated by independent point mutations in the two alleles of the p85alpha gene: one in the coding sequence, and the other in the acceptor sequence for splicing. Introduction of wild-type p85alpha into HCC2998 cells induced slight rounding of the cells and enhancement of mucin secretion. At the same time, a membrane receptor, ErbB3, was phosphorylated on tyrosine, which in turn, binds to PI3' kinase. Since ErbB3 is upstream of PI3' kinase, it is likely that there is an autocrine loop in which PI3' kinase is activated by ErbB3, which may contribute to dedifferentiation of the cells.

Alleles↗
PubMed2006

Inverted ductal papilloma of minor salivary gland: case report with immunohistochemical study and literature review.

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.

Biomarkers, Tumor↗
PubMed2005

p600, a unique protein required for membrane morphogenesis and cell survival.

In this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin scaffold. In the cytoplasm, p600 and clathrin form a meshwork structure, which could contribute to cytoskeletal organization and membrane morphogenesis. Reduced expression of p600 with interference RNA abrogates integrin-mediated ruffled membrane formation and, furthermore, prevents activation of integrin-mediated survival pathways. Consequently, knockdown of p600 sensitizes cells to apoptosis induced by cell detachment. These findings provide mechanistic insight into the regulation of membrane-proximal events in tumorigenesis.

Apoptosis↗
PubMed2005

Clinical features of third open-heart valve surgery at the same valve position.

OBJECTIVE: Recently, there has been an increase in case of repeated open-heart valve surgery and the clinical results of the second surgery are only slightly worse than those of the first surgery. However, clinical results of the third open-heart valve surgery at the same position are rarely reported. Clinical features of third open-heart valve surgery at the same position are discussed in this study. METHODS: Between 1995 and 2004, 16 patients underwent third open-heart valve surgery at the same valve position under cardiopulmonary bypass. The average age of the 16 patients, 12 females and 4 males, was 56 +/- 15 years. Clinical features of the 16 cases were retrospectively analyzed. RESULTS: Mechanical valve nonstructural dysfunction was the most common valve malady, followed by bioprosthetic valve dysfunction. The duration of surgery from skin incision to establishment of the cardiopulmonary bypass was 94 +/- 42 minutes. Myocardial ischemia time was 137 +/- 38 minutes and extracorporeal circulation time was 212 +/- 82 minutes. Early mortality was seen in 1 patient (6.25%) and late mortality was seen in 1 patient. CONCLUSION: Mechanical valve nonstructural valve dysfunction leads to repeated valve surgery. The clinical results of the third open-heart valve surgery at the same valve position are acceptable, and the mid-term survival is excellent.

Adult↗
PubMed2005

The CarboMedics prosthetic heart valve: experience with 180 implants.

At Jichi Medical School Hospital, three types of mechanical prosthetic valves (CarboMedics, Omnicarbon, Bicarbon) were used without randomization from 1991 to 2000. A retrospective study of valve replacements done between June 1991 and November 2000 utilizing 180 CarboMedics valves in 145 patients who had not previously undergone prosthetic valve replacement or aortic root and/or arch replacement was conducted to evaluate midterm patient outcomes to assess the future continuous use of CarboMedics valves. Women made up 47.6% of the patients and the mean age was 57.5 years (range 12-80 years). Preoperative New York Heart Association functional class was III or IV in 92.4% (134/145) of patients. Mean follow-up of 4.5 years (range 0-10.0 years) was 95.9% complete, with a total of 628 patient-years (PY). Early (within 30 postoperative days) mortality was 5.5% (8 of 145): 3 from hemorrhage, 3 from nonvalve-related heart failure, 1 from infection, and 1 from arrhythmia. There were 16 late deaths (2.54%/PY): 1 from hemorrhage, 4 from unknown causes/sudden death, 4 from nonvalve-related heart failure, and 7 from other noncardiac causes. A total of 121 patients (83.0%) were alive at the last follow-up, done in November 2000. The linearized death rate was 3.82%/year (including 1.11%/year for valve-related deaths). Linearized death rates from various causes were: bleeding, 0.96%/year; thromboembolism, 1.11%/year; thrombosis, 0.39%/year; perivalvular leak, 0.96%/year; endocarditis, 0%/year; hemolysis, 0%/year; and reoperation, 0.63%/year. No structural valve failure was observed. Comparative early mortality rates of valve replacement without aortic root replacement or arch replacement, excluding repeat valve replacement operations, in our institute, were 3.5% (12/307) for all valve types used contemporaneously, 2.6% (2/76) for Omnicarbon valves, and 2.3% (2/86) for Bicarbon valves. Although the CarboMedics valve had a rather high mortality rate of 5.5% (8/145) compared with the total early mortality rate of 3.5%, the low incidence of valve-related complications might support the continued use of the CarboMedics valve for valve replacement.

Adolescent↗
PubMed2004

Histological analysis of the ligamentum flavum of patients with dialysis-related spondyloarthropathy.

Dialysis-related spondyloarthropathy (DRS) is a severe complication of long-term hemodialysis that ultimately leads to functional disability of the upper and lower extremities. Although the cause of this disease is still unknown, it is thought that amyloid deposits are involved. beta2-Microglobulin (beta2M) is a major component of amyloid fibrils, some of which are modified with the advanced glycation end-product (AGE). To clarify the pathophysiology of DRS we histologically examined the ligamentum flavum of the cervical spine in 15 patients with DRS. The mean duration of hemodialysis was 20 years (12-27 years). In addition to the congo red stain for amyloid, beta2M and AGE were detected by immunohistochemical methods. Macrophages were stained with CD68 antibody. Amyloid deposits were found in tissues, although the extent of the stained area differed among the patients. Part of the amyloid deposit area was positively immunostained for beta2M and AGE. In 10 cases macrophages positive for CD68 infiltrated around the amyloid deposits. Comparing these histological findings with the dialysis duration, more positive staining areas for beta2M and AGE were found in the tissue from patients with long-term dialysis. These findings suggest that both beta2M and AGE play roles in the pathogenesis of DRS.

Adult↗
PubMed2004

Successful weaning from cardiac extracorporeal membrane oxygenation by banding a hemodialysis arteriovenous fistula.

We report a case in which weaning from cardiac extracorporeal membrane oxygenation (ECMO) was achieved by temporarily occluding the hemodialysis arteriovenous fistula. A 68-year-old man with diabetic nephropathy underwent coronary artery bypass surgery, and cardiac ECMO was used to wean the patient from cardiopulmonary bypass. An ultrasonic flowmeter showed the arteriovenous flow to be over 750 ml/min, which can lead to increased preload on the weakened heart. On the sixth postoperative day, occlusion of the fistula by compression with a soft bandage provided the correct balance between myocardial reserve and shunt volume and hence facilitated successful weaning from cardiac ECMO.

Aged↗
PubMed2003

The PI 3-kinase-Rac-p38 MAP kinase pathway is involved in the formation of signet-ring cell carcinoma.

Signet-ring cell carcinoma is classified in poorly differentiated adenocarcinoma with an aggressive nature and a poor prognosis. We have shown that the activation of PI 3-kinase in highly differentiated adenocarcinomas induces loss of cell-cell contact and formation of vacuoles, giving phenotypes similar to those of signet-ring cell lines. SB203580, a potent p38 MAP kinase inhibitor, blocked this transition, and expression of an active form of MKK6 (MKK6DA), an activator of p38 MAP kinase, gave effects similar to those induced by expression of the active form of PI 3-kinase (BD110), although formation of large vacuoles was not induced. Activation of MKK3, another activator of p38 MAP kinase, was activated in native signet-ring carcinoma cell lines. Anchorage-independent growth of signet-ring cell lines was inhibited by LY294002 or SB203580. These results suggest that p38 MAP kinase is functioning downstream of PI 3-kinase in signaling of the malignant phenotype. Secretion of mucins was enhanced in BD110-expressing cells, but not in MKK6DA-expressing cells, suggesting that secretion of mucins is independent of the MKK6-p38 MAP kinase cascade. Thus, there may be at least two pathways, p38 MAP kinase-dependent and -independent, which are involved in regulation of cell-cell contact and the protein secretion system, respectively.

Adenocarcinoma↗
PubMed2003

When and how does nonstructural mechanical prosthetic heart valve dysfunction occur?

OBJECTIVE: We discuss the clinical aspects related to mechanical valve dysfunction based upon 20 years' experience of our cases. METHODS: Between January 1982 and December 2001, 21 patients underwent surgical interventions because of mechanical valve dysfunction. Thirteen men and 8 women (mean age 47 +/- 20, range 3-75 years-old), were included. RESULTS: Mitral valve dysfunction was observed in 12 patients. Prosthetic valve stenosis occurred in 6 patients between 2 and 224 months, and paravalvular leaks in 4 between 1 and 71 months after surgery. The other 2 patients suffered from hemolytic anemia with mild paravalvular leaks between 102 and 104 months after surgery. Aortic valve dysfunction was observed in 8 patients including 3 stenotic lesions between 48 and 97 months and 5 paravalvular leaks between 3 and 150 months after surgery. Tricuspid regurgitation was seen in 1 patient with a huge right atrium at 42 months after surgery. Early death was seen in 1 patient. Late death occurred in 1 patient, 17 years after operation. Survival, including early death, was 95.2%, at 10 and 15 years. One valve-related complication of bioprosthetic valve endocarditis at the mitral and tricuspid positions occurred 12 years after a reoperation. The freedom from complications was 95.2% at 10 years, and 76.2% at 15 years. CONCLUSIONS: Paravalvular leaks without overt endocarditis had latency periods of up to 12 years, and pannus formation was observed 20 years after surgery. Early and late clinical results after surgery for mechanical valve dysfunction were excellent.

Adolescent↗
PubMed2003

Levels of fibroblast growth factor 2 in synovial fluids in human patients with internal derangement of the temporomandibular joint.

OBJECTIVE: We sought to elucidate the levels of fibroblast growth factor 2 (FGF-2) in synovial fluid taken from internally deranged human temporomandibular joints (TMJs) and to discuss the role of FGF-2 in the pathogenesis of internal derangement. STUDY DESIGN: Through the use of a pumping procedure, diluted synovial fluid was collected from the upper joint compartment of 22 TMJs with evidence of internal derangement (21 patients) and 8 TMJs with no such evidence (5 control subjects). Two of the control subjects were patients who had habitual dislocation, and three were healthy volunteers. The level of FGF-2 in the synovial fluid was assessed by means of an enzyme-linked immunosorbent assay. RESULTS: FGF-2 levels were at detectable levels in 15 of the 22 TMJs (68%) with internal derangement. The mean concentration of FGF-2 was 24 pg/mL. In the control group, FGF-2 levels were detectable in only 1 of 8 joints (13%), for a concentration of 3 pg/mL. The mean concentration of FGF-2 in the synovial fluid was significantly higher in the internal derangement group than in the control group (P =.02). CONCLUSIONS: FGF-2 levels are elevated in the human synovial fluid of TMJs with internal derangement.

Adolescent↗
PubMed2003

Prostaglandin E1 but not corticosteroid increases nerve root blood flow velocity after lumbar diskectomy in surgical patients.

The purpose of this study was to clarify whether prostaglandin E1 (PGE(1)) or corticosteroid could increase blood flow in the nerve root because neurologic symptoms in spinal stenosis may be based on the vascular insufficiency in the nerve root. Fifty-seven patients undergoing lumbar diskectomy were randomly assigned to one of three groups. Each group received one of three protocols for intravenous injection: 10 mL of saline solution, group A (n = 19); 10 mL of PGE(1) (20 microg) solution, group B (n = 19); and 10 mL of dexamethasone (8 mg) solution, group C (n = 19). After lumbar diskectomy, a probe for laser Doppler flowmetry was placed directly on the lumbar nerve root. Nerve root blood flow (RBF) velocity and mean arterial pressure (MAP) were measured before injection (T0), 5 minutes after the start of injection (T1), 10 minutes after the start of injection (T2), and 10 minutes after the end of injection (T3). In groups A and C, these did not change throughout the time course. In group B, MAP decreased significantly at T1 (92%; P <.001), T2 (89%; P <.0001), and T3 (91%; P <.0001), while RBF velocity increased significantly at T1 (125%; P <.05), T2 (128%; P <.05), and T3 (121%; P <.05) compared with T0. The values in group B were different from those in group A (P <.05) and group C (P <.05) at T1 and T2. The results show that intravenous injection of low-dose PGE(1), but not corticosteroid, increases RBF velocity after lumbar diskectomy.

Adrenal Cortex Hormones↗
PubMed2002

Paravalvular leakage causing hemolytic anemia at 8-9 years after mitral valve replacement.

We report two similar cases of women, aged 52 and 71 years, who developed shortness of breath or easy fatigability at 8-9 years after mitral valve replacement of the mitral valve in each patient, the echocardiographic study revealed paravalvular leakage. Previous examination before the appearance of symptoms had revealed a well-functioned prosthetic valve, and no hematological abnormality had been detected. The hemoglobin levels at admission were 6.4 and 6.6 g/dl, and their serum lactate dehydrogenase levels were 5218 and 4608 mU/ml. Each successfully underwent another valve replacement, and after surgery, the hemolytic anemia and the symptoms disappeared.

Aged↗
PubMed2002

Single-center experience with the bicarbon bileaflet prosthetic heart valve in Japan.

We analyzed midterm results using the Bicarbon valve in a single center. Forty-four patients had aortic valve replacement (AVR), 48 had mitral valve replacement (MVR), and 13 had both aortic and mitral valve replacement (DVR). The mean age of the 105 patients was 61.2 +/- 11.3 years. The mean follow-up was 1.8 +/- 1.1 years with a cumulative follow-up of 188 patient-years. There were 5 early deaths (4.7%: 4 in the AVR group and 1 in the MVR group) and 5 late deaths (2.7% per patient-year: 3 malignancy, 1 cerebral hemorrhage, 1 myocardial infarction). Survival at 3 years was 91 +/- 4% in the AVR group, 92 +/- 5% in the MVR group, and 66 +/- 23% in the DVR group. The linearized incidence of thromboembolic complications, hemorrhagic complications, and paravalvular leaks in all patients was 1.06 +/- 2.34%, 1.60 +/- 2.53%, and 0.53 +/- 2.22% per patient-year, respectively. No other complications were observed. In conclusion, the Bicarbon prosthetic heart valve has shown excellent clinical results associated with a low incidence of valve-related complications.

Aged↗
PubMedDate not supplied

Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity.

Conventional and novel protein kinase C (PKC) isozymes contain two cysteine-rich C1 domains (C1A and C1B), both of which are candidate phorbol-12, 13-dibutyrate (PDBu)-binding sites. We synthesized C1 peptides of 50-70 residues corresponding to all PKC isozyme C1 domains using an Fmoc solid-phase strategy. These C1 peptides were successfully folded by zinc treatment, as monitored by electrospray ionization time-of-flight mass spectrometry. We measured the K(d)'s of [3H]PDBu for all PKC C1 peptides. Most of the C1 peptides, except for delta-C1A and theta-C1A, showed strong PDBu binding affinities with K(d)'s in the nanomolar range (0.45-7.4 nM) comparable with the respective whole PKC isozymes. The resultant C1 peptide library can be used to screen for new ligands with PKC isozyme and C1 domain selectivity. Non-tumor-promoting 1-oleoyl-2-acetyl-sn-glycerol and bryostatin 1 showed relatively strong binding to all CIA peptides of novel PKCs (delta, epsilon, and eta). In contrast, the tumor promoters (-)-indolactam-V, ingenol-3-benzoate, and PDBu bound selectively to all C1B peptides of novel PKCs. The preference of tumor promoters for the domain might be related to tumorigenesis since recent investigations proposed the involvement of novel PKCs in tumor promotion in vivo using transgenic or knockout mice. Moreover, we recently have found that a new lactone analogue of benzolactams (6) shows significant selectivity in PKCeta-C1B binding.

Binding Sites↗
PubMedDate not supplied

Twenty-two year experience with the omniscience prosthetic heart valve.

This study was designed to evaluate the long-term clinical results of the Omniscience tilting disc valve. Omniscience valves were implanted in 51 patients (mean age, 50 +/- 10 years); 18 had aortic valve, 24 had mitral valve, and 9 had both aortic and mitral valve replacements. Oral warfarin potassium and dipyridamole were prescribed as our anticoagulant therapy. Preoperatively, 42 patients were in New York Heart Association class III or IV, and 23 of 25 surviving patients were in class I or II after operation. There were 2 (3.9%) early deaths and 23 late deaths (3.5 +/- 0.7% per patient-year). Cardiac related mortality including congestive heart failure, sudden death, and thromboembolism, and hemorrhagic complications were seen in 16 patients. Overall survival at 10, 15, and 20 years was 77 +/- 6%, 62 +/- 7%, and 46 +/- 7%, respectively. Thromboembolic complications were seen in 5 patients, for a rate of 0.8 +/- 0.3% per patient-year; similarly, hemorrhagic complications were also seen in 5 patients. Nonstructural prosthetic valve dysfunction was seen in 4 patients, for a rate of 0.6 +/- 0.3% per patient-year, and sudden death was seen in 2, a rate of 0.3 +/- 0.2% per patient-year. The Omniscience prosthesis demonstrated excellent postoperative clinical status with low rates of valve related complications.

Adult↗