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Biomedical subjects

Hiroyuki Tanaka

Publications and source records attributed to Hiroyuki Tanaka.

At least 181 records · Page 10Linked to original sources
PubMed2003

PTHrP rescues ATDC5 cells from apoptosis induced by FGF receptor 3 mutation.

UNLABELLED: An activation mutation in the FGFR3 gene causes ACH. The effects of the FGFR3 mutants on apoptosis were analyzed in a chondrogenic cell line. ACH chondrocytes exhibited marked apoptotic with downregulation of PTHrP expression. Rescue of these cells by PTHrP replacement implies a potential therapy for this disorder. INTRODUCTION: Achondroplasia (ACH), the most common form of short-limb dwarfism, and its related disorders are caused by constitutively activated point-mutated FGFR3. Recent studies have provided a large body of evidence on chondrocyte proliferation and differentiation in these disorders. However, little is known about the possible effects of the FGFR3 mutants on apoptosis of chondrocytes. METHODS: The mutant FGFR3 genes causing ACH and thanatophoric dysplasia (TD), which is a more severe neonatal lethal form, were introduced into a chondrogenic cell line, ATDC5. Analysis of apoptosis was estimated by TUNEL assay, DNA laddering, and fluorescent measurement of mitochondrial membrane potential. Expression levels of parathyroid hormone-related peptide (PTHrP) and apoptosis-related genes were analyzed by Northern blot or immunoblot. RESULTS: The introduction of these mutated FGFR3s into ATDC5 cells downregulated PTHrP expression and induced apoptosis with reduction of Bcl-2 expression. Importantly, replacement of PTHrP prevented the apoptotic changes and reduction of Bcl-2 expression in ATDC5 cells expressing the ACH mutant. In parallel with the severity of disease and the activity of FGFR3, ATDC5 cells expressing TD-mutant FGFR3 showed less expression of PTHrP and Bcl-2 and induced more remarkable apoptotic changes compared with ACH-mutant expressing cells. Furthermore, overexpression of Bcl-2 inhibited apoptotic changes, suggesting that the mutant FGFR3 caused apoptosis, at least in part, through reduction of Bcl-2 expression, which seems to be downstream of PTHrP. CONCLUSIONS: Our data suggest that excessive activation of signaling cascades mediated by the FGFR3 mutants inhibits the expression of PTHrP and Bcl-2, resulting in apoptosis of chondrocytes, possibly leading to short-limb dwarfism. Rescue of these cells by PTHrP replacement implies a potential therapy for this disorder.

Achondroplasia↗
PubMed2003

Decreased plasma brain natriuretic peptide levels after a successful maze procedure.

BACKGROUND AND AIM OF THE STUDY: Previous reports indicate that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in atrial fibrillation (AF), but decrease after successful direct current (DC) cardioversion. Although the maze procedure is the only curative therapy for AF, the effects on atrial and left ventricular function remain unclear. The study aim was to determine whether plasma ANP and BNP levels decrease after the maze procedure in patients with mitral valve disease. METHODS: Twenty-seven patients either with (n = 23) or without (n = 4) AF underwent mitral valve surgery; of these patients, 13 underwent a maze procedure for chronic AF. Blood samples and echocardiographic data were obtained before and at one year after surgery. RESULTS: Ten patients with AF achieved sinus rhythm (SR) or junctional rhythm after the maze procedure. In patients subjected to mitral valve surgery, mean plasma levels of ANP and BNP were 59.8 +/- 11.9 and 139.2 +/- 53.7 pg/ml, respectively. ANP and BNP plasma levels fell significantly after surgery (to 32.1 +/- 4.1 and 46.7 +/- 10.2 pg/ml, respectively; p = 0.04 and p = 0.004). In patients with successful maze procedure, plasma levels of BNP and left ventricular end-diastolic dimension (LVDd) were significantly decreased by 35.7% and 82.7% compared with preoperative values (BNP, 35.7 +/- 4.9% for SR versus 83.4 +/- 9.6% for AF, p = 0.008; LVDd, 82.7 +/- 3.7% for SR versus 97.0 +/- 3.2% for AF, p = 0.0159). CONCLUSION: A successful maze procedure significantly decreased LVDd and plasma levels of BNP after surgery. These results show that the maze procedure is effective in improving left ventricular diastolic dysfunction for a mid-term period in patients with mitral valve disease.

Adult↗
PubMed2003

[Perioperative management of a morbidly obese patient with sleep apnea syndrome].

A 34-year-old male, weighing 110 kg, with severe obstructive sleep apnea syndrome (OSAS) was urgently taken to the hospital for heart and respiratory failure. His body mass index was 39, showing that he was mobidly obese. He was scheduled for tonsillectomy under general anesthesia. BiPAP (bi-level positive airway pressure) system was applied for respiratory assist. He went on a diet to prepare for the surgery. Preoperative examination revealed that the neck was short, and the tongue and tonsils were hypertrophic. Since we expected difficulty in maintaining upper airway open during the perioperative period, anesthesia was induced with fentanyl and propofol, and fiberscopic intubation was performed by preserving spontaneous breathing. Postoperatively he was taken to the intensive care unit and was mechanically ventilated for 6 days because pharyngeal edema could aggravate his respiratory condition when extubated just after the surgery. He was successfully extubated and BiPAP was applied in the same day. We recommend that the patient with morbidly obese OSAS should be cared intensively during perioperative period.

Adult↗
PubMed2003

[Prosthetic valve endocarditis caused by Streptococcus constellatus infection complicated with perivalvular abscess: serial observation by transesophageal echocardiography: a case report].

A 61-year-old man was admitted to an associated hospital because of fever. He had undergone aortic valve and mitral valve replacement 6 years ago, because of rheumatic aortic valve stenosis, and mitral valve stenosis and regurgitation. He had prosthetic valve endocarditis caused by a rare Streptococcus constellatus infection complicated by multiple organ failure and systemic embolism. We considered that surgical treatment was difficult, and continued antibiotic treatment. The inflammatory reaction and fever improved. Prosthetic valve endocarditis is often difficult to identify and treat. Streptococcus constellatus infection is characterized by destruction and formation of abscess. We followed up the patient by transesophageal echocardiography, and observed the course of change of the paravalvular abscess around the aortic valve from echogenic to echolucent.

Abscess↗
PubMed2003

[Inflammatory pseudotumor of the urinary bladder diagnosed using 3D-CT cystoscopy].

Inflammatory pseudotumor of the urinary bladder is a rare benign entity of the submucosal stroma that can easily be mistaken for a malignant neoplasm both clinically and histologically. We report a case of an inflammatory pseudotumor of the urinary bladder in which 3D-CT cystoscopy aided in the diagnosis. A 38-year-old man presented with persistent miction pain, penile pain, and dysuria despite symptomatic treatment at another hospital. Cystoscopic examination, MRI and 3D-CT cystoscopy revealed a 3.0 X 3.0 cm wide-based nonpapillary tumor located at the anterior dome of the urinary bladder. Transabdominal biopsy and transurethral resection were performed and the tumor was suspected to be transitional cell carcinoma. A partial cystectomy and urachus excision were then performed for suspected urachal tumor based upon the radiological examinations. Careful examination of the specimen revealed an inflammatory pseudotumor. We discuss 20 cases of inflammatory pseudotumor of the urinary bladder including ours.

Adult↗
PubMed2003

[PTH and immobilization induced osteopenia].

Decreased bone mass in the astronauts indicates that the gravity force is an important factor for bone physiology. Similarly, prolonged immobilization, such as bed-rest, induces severe osteopenia and pathological fracture. Recently the molecular mechanisms by which mechanical stress increases bone mass and immobilization induces osteopenia have been elucidated. In this manuscript, this molecular mechanism of the immobilization induced osteopenia and the promising roles of PTH in the pathogenesis and treatment of the immobilization induced osteopenia will be discussed briefly.

English Abstract↗
PubMed2003

[PTH in the treatment of achondroplasia].

To improve adult height in the patients with achondroplasia, we have been analyzing molecular mechanism of the growth cartilage differentiation. During this approach, we identified PTH/PTHrP as an important regulatory factor in cartilage differentiation. The manipulation of the PTH/PTHrP activity may serve as a new therapeutic modality.

English Abstract↗
PubMed2002

The fission yeast pfh1(+) gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase.

The Cdc24 protein plays an essential role in chromosomal DNA replication in the fission yeast Schizosaccharomyces pombe, most likely via its direct interaction with Dna2, a conserved endonuclease-helicase protein required for Okazaki fragment processing. To gain insights into Cdc24 function, we isolated cold-sensitive chromosomal suppressors of the temperature-sensitive cdc24-M38 allele. One of the complementation groups of such suppressors defined a novel gene, pfh1(+), encoding an 805 amino acid nuclear protein highly homologous to the Saccharomyces cerevisiae Pif1p and Rrm3p DNA helicase family proteins. The purified Pfh1 protein displayed single-stranded DNA-dependent ATPase activity as well as 5' to 3' DNA helicase activity in vitro. Reverse genetic analysis in S.pombe showed that helicase activity was essential for the function of the Pfh1 protein in vivo. Schizosaccharomyces pombe cells carrying the cold-sensitive pfh1-R20 allele underwent cell cycle arrest in late S/G2-phase of the cell cycle when shifted to the restrictive temperature. This arrest was dependent upon the presence of a functional late S/G2 DNA damage checkpoint, suggesting that Pfh1 is required for the completion of DNA replication. Furthermore, at their permissive temperature pfh1-R20 cells were highly sensitive to the DNA-alkylating agent methyl methanesulphonate, implying a further role for Pfh1 in the repair of DNA damage.

Adenosine Triphosphatases↗
PubMed2002

Size distribution measurement of vesicles by atomic force microscopy.

Vesicles have been utilized as nanoscale vehicles for reagents including potential drug delivery systems. When used to deliver drugs, vesicle size and the size distribution are important factors in the determination of the dosage, cell specificity, and rate of clearance from the body. Current size measurement techniques for vesicles are electron microscopy and dynamic light scattering, but their results are not equal. Therefore atomic force microscopy was attempted as another size measurement technique. After adsorption of the vesicles from a low-concentration solution of vesicles on mica substrate, each vesicle is generally found as a flattened structure. The diameters of vesicles in these solutions and their distribution have been successfully estimated from the surface area of the flattened structure of each vesicle. At higher concentrations, we have found a monolayer crammed with dome-shaped vesicles on the substrate. The diameters of vesicles in these solutions have also been successfully estimated from the surface area of the dome-shaped structure of each vesicle. Diameters of vesicles in solution estimated from two different vesicle concentrations are not close to those reported by electron microscope studies but are close to those reported by dynamic light scattering studies.

Adsorption↗
PubMed2002

Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes following Fcepsilon receptor I cross-linking: an interspecies comparison.

Rodent mast cells (MCs) are common experimental tools but are somewhat different from their human counterparts in their responses to certain cytokines and drugs. We examined the expression of more than 10 000 distinct genes in human and mouse cultured MCs using high-density oligonucleotide probe arrays to find molecules similarly regulated and expressed by the 2 MC types. After stimulation via high-affinity Fcepsilon receptor I (FcepsilonRI), the transcriptional levels of several CC chemokines were markedly increased, and I-309 (CCL1), macrophage inflammatory protein-1alpha (MIP-1alpha) (CCL3) and MIP-1beta (CCL4) were found among the 10 most increased human and mouse transcripts from approximately 12 000 genes (including some expressed sequence tags). In addition, a costimulatory molecule that was originally found on the membrane of activated T cells, 4-1BB (CD137), was found among the 10 most increased transcripts. The FcepsilonRI-induced expression of CC chemokines and 4-1BB was also detected at the protein level in both MC types. The conservation of these responses suggests that MCs play a crucial role in recruitment of various CCR-expressing cells into the tissue in a manner dependent on immunoglobin E, and that FcepsilonRI-mediated induction of several CC chemokines and 4-1BB is highly conserved between human and mouse. Interspecies comparison studies at the whole genome expression level should be useful for the interpretation of experimental data obtained in animal models of human pathobiology.

Animals↗
PubMed2002

Cytoplasmic p21(Cip1/WAF1) regulates neurite remodeling by inhibiting Rho-kinase activity.

p21(Cip1/WAF1) has cell cycle inhibitory activity by binding to and inhibiting both cyclin/Cdk kinases and proliferating cell nuclear antigen. Here we show that p21(Cip1/WAF1) is induced in the cytoplasm during the course of differentiation of chick retinal precursor cells and N1E-115 cells. Ectopic expression of p21(Cip1/WAF1) lacking the nuclear localization signal in N1E-115 cells and NIH3T3 cells affects the formation of actin structures, characteristic of inactivation of Rho. p21(Cip1/WAF1) forms a complex with Rho-kinase and inhibits its activity in vitro and in vivo. Neurite outgrowth and branching from the hippocampal neurons are promoted if p21(Cip1/WAF1) is expressed abundantly in the cytoplasm. These results suggest that cytoplasmic p21(Cip1/WAF1) may contribute to the developmental process of the newborn neurons that extend axons and dendrites into target regions.

3T3 Cells↗
PubMed2002

Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach.

The roles of CDX2 and CDX1 homeobox genes during gastric carcinogenesis remain poorly defined. We have studied the expression of CDX2/1 in gastric cancers and intestinal metaplasia (IM) of 69 gastric carcinoma patients by immunohistochemistry. CDX2/1 were shown to be ectopically overexpressed in IM in 41 (85%) of 48, and 47 (90%) of 52 cases, respectively. The expression of CDX2/1 was detected in 38 (55%) and 51 (74%) of the 69 gastric carcinomas, respectively. The histological type of the gastric carcinomas was independently associated with CDX2 expression, but not with that of CDX1, with higher CDX2 expression in intestinal type (differentiated type) than in diffuse type (undifferentiated type) gastric carcinomas. Our results thus suggest that CDX2 and CDX1 may play a role during IM formation and gastric carcinogenesis.

Animals↗
PubMed2002

Simple assay for antitumour immunoactive glycoprotein derived from Chlorella vulgaris strain CK22 using ELISA.

A quantitative ELISA system was developed using a monoclonal antibody (MAb) specific for an antitumour immunoactive glycoprotein (CVS) derived from C. vulgaris strain CK22. The full measuring range of the assay extends from 0.63 to 10.0 ng/mL of CVS. Although no cross-reaction was observed to proteins tested or other biological response modifiers (BRMs) derived from different sources, cross-reactions were found with culture supernatants from two other strains of C. vulgaris having a strong antitumour immunoactivity. Treatment of CVS with protease, acid or alkali weakened or completely eliminated the reactivity against the MAb and also its antitumour immunoactivities. This ELISA system is suitable for the biologically active form of CVS derived from C. vulgaris strain CK22 and related immunoactive strains.

Algal Proteins↗
PubMed2002

Temporary and permanent biventricular pacing via left ventricular epicardial leads implanted during primary cardiac surgery.

OBJECTIVES: Biventricular pacing (BVP) is a new strategy for treating patients with severe congestive heart failure (CHF) and intraventricular conduction delay, but its full potential and technicalities of BVP require further evaluation. We evaluated BVP benefits in 4 patients in whom we implanted a left ventricular lead during primary cardiac surgery. METHODS: Four CHF patients treated surgically between October 2000 and August 2001 underwent, at primary surgery, the implantation of leads in the right atrium, right ventricle, and left ventricle (LV) for postsurgical BVP. All patients had severe LV dysfunction and dilatation with intraventricular conduction delay. Surgeries involved CABG alone (n = 1), CABG + Dor's operation (n = 2), and tricuspid valve replacement + Maze procedure (n = 1). BVP was begun immediately after surgery in all 4 patients. Hemodynamic variables with BVP were compared to those without BVP for each patient, and the utility and technical aspects of implantation were evaluated. RESULTS: BVP increased mean systemic blood pressure by 11% and mean LV stroke work index by 19% in the acute postsurgery period, and reduced mitral regurgitation. Two of the patients were implanted with a generator for permanent BVP, one at 1 month and the other at 6 months after surgery. The threshold of the LV epicardial lead of these 2 patients was below 2 V during follow-up, and BVP was successful. CONCLUSIONS: Temporary BVP during the short-term after cardiac surgery improved cardiac function and decreased mitral regurgitation in all 4 of our patients. Epicardial lead implantation may thus be a useful option during surgical treatment of patients with CHF and intraventricular conduction delay if long-term permanent BVP is indicated.

Aged↗
PubMed2002

Biventricular pacing in a patient with severe congestive heart failure.

We report a case of dilated cardiomyopathy with severe congestive heart failure (ejection fraction: 19%) and complete left bundle branch block (QRS duration: 240 ms) 13 years after aortic valve replacement. Permanent biventricular pacing was implanted by inserting a left ventricular lead thorough a small left thoracotomy following intravenous insertion of right atrial and ventricular endocardial leads. Biventricular pacing increased hemodynamic parameters such as blood pressure, cardiac output and decreased mitral regurgitation. Symptoms and exercise tolerance improved dramatically. Left ventricular epicardial lead insertion via a small thoracotomy is thus useful in selected patients.

Aortic Valve↗