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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer.

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.

Adenocarcinoma↗
PubMed2005

The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation.

Hyaluronan (HA) is one of the major extracellular matrix components in cartilage. In addition to the biomechanical functions, HA has various important roles in the differentiation of chondrocytes. The purpose of this study was to clarify the nature of HA synthesis during chondrocyte differentiation. Growth plate chondrocytes were isolated from rabbit ribs and cultured in chondrocyte differentiation medium. The amount of HA and HA synthase (HAS) mRNA levels were analyzed for each stage of chondrocyte differentiation by means of high-performance liquid chromatography (HPLC) and real-time PCR, respectively. The distribution of HA in cultured chondrocytes was observed by histochemical staining. The amount of HA, ranging widely in size, was increased substantially during the hypertrophic stage. The expression levels of HAS2 and HAS3 mRNAs were low during the matrix-forming stage. HAS2 mRNA level was substantially enhanced at the pre-hypertrophic stage, whereas HAS3 mRNA level exhibited a slight increase. HAS1 mRNA was not detected. The intensity of HA staining was high around the hypertrophic chondrocytes. These results suggest that HA metabolism in chondrocyte differentiation is regulated by the selective expression of HASs, and HAS2 and the related large size-HA may have a certain association with the hypertrophic changes of chondrocytes.

Animals↗
PubMed2005

Characteristics of metachronous multiple early gastric cancers after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) of early gastric cancer is a minimally invasive procedure. The incidence and characteristics of metachronous multiple gastric cancers were investigated in a retrospective study in patients with early gastric cancer after EMR treatment. PATIENTS AND METHODS: A total of 143 patients with early gastric cancer who had undergone EMR treatment were periodically followed up with endoscopic examinations for 24 months or longer. RESULTS: The median period of endoscopic follow-up was 57 months (range 24 - 157 months). None of the patients died of gastric cancer, and there were no treatment-related deaths. Five patients died of other diseases. Of 20 patients (14 %) with metachronous multiple gastric cancers, 15 were treated by EMR. One patient with differentiated submucosal cancer and four with undifferentiated cancers underwent surgery. Sixteen patients (11 %) had synchronous multiple early gastric cancer lesions within 1 year of the initial EMR. About half of the multiple lesions were located in the same third of the stomach as the primary lesion, and most lesions were similar in macroscopic type to the primary lesions. Most multiple lesions were of the differentiated type. CONCLUSIONS: Annual endoscopic examinations can preserve the whole stomach in most patients with early gastric cancer after successful EMR.

Adenocarcinoma↗
PubMed2005

Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel.

The association between mechanical stimulation and chondrocyte homeostasis has been reported. However, the participation of PTHrP (parathyroid-hormone-related protein) in the mechano-regulation of chondrocyte metabolism remains unclear. We determined whether mechanical stimulation of chondrocytes induces the expression of PTHrP and, further, whether the mechano-modulation of PTHrP is dependent on the maturational status of chondrocytes. Cyclic mechanical strain was applied to rat growth plate chondrocytes at the proliferating, matrix-forming, and hypertrophic stages at 30 cycles/min. Cyclic mechanical strain significantly increased PTHrP mRNA levels in chondrocytes at the proliferating and matrix-forming stages only. The induction of PTHrP was dependent on loading magnitude at the proliferating stage. Using specific ion channel blockers, we determined that mechano-induction of PTHrP was inhibited by nifedipine, a Ca2+ channel blocker. These results suggest that mechanical induction of PTHrP possibly provides the environment for greater chondrocyte replication and matrix formation that would subsequently affect cartilage formation.

Animals↗
PubMed2005

[New technique to determine graft length using the proximal anastomotic system during off-pump coronary artery bypass grafting].

For determining the graft length for an aortic connector, grafts to the circumflex (Cx) and the posterior descending (PD) regions often present problems. Difficulties in determining the appropriate distance between the aorta and coronary artery have been reported to be due to changes in the morphology of the heart following the evolution of Cx and PD. We set an intermediate point (IMP) in advance and then determine graft distance in 2 steps. When using the IMP method, determination of the graft length in the Cx region is not difficult. However, attention should be paid to determine the distance between the IMP and anastomosed site without deforming the heart, as the graft length becomes shorter if the heart as a whole is pulled up by traction of the diaphragm during evolution to the PD region.

Coronary Artery Bypass, Off-Pump↗
PubMed2005

[Left atrial sarcoma with the initial diagnosis of myxoma].

Primary tumors of the heart are rare. The majority of these tumors are benign, with myxomas located in the left atrium being the most common form. Almost all malignant tumors are sarcomas and occur preferentially in the right side of the heart. The case of a 73-year-old woman who presented with symptoms of mitral valve stenosis is reported. Echocardiography revealed a left atrial mass that was interpreted as atrial myxoma. At the operation, the tumor which was lobulated and had a smooth surface was arising from posterior wall of left atrium extending into the mitral annulus. Wide surgical excision was possible with left atrial reconstruction and mitral valve replacement. Histological and immunohistochemical studies revealed malignant undifferentiated sarcoma extending to the surface of mitral valve. Postoperative metastatic work-up showed no evidence of dissemination. The patient survived the operation without adjuvant radiation and chemotherapy and has been symptom-free over 1 year. At present, 16 months following the operation, the patient is alive with no evidence of disease.

Aged↗
PubMed2004

Decrease in cortical benzodiazepine receptors in symptomatic patients with leukoaraiosis: a positron emission tomography study.

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.

Aged↗
PubMed2004

Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint.

Hyaluronan (HA) synthesis in the synovial membrane is affected by various chemical mediators. It is hypothesized that transforming growth factor-beta 1 (TGF-beta 1) would be a mediator to modulate HA synthesis in cultured synovial membrane fibroblasts of the temporomandibular joint (TMJ). Fibroblasts were extracted from the TMJ synovial membrane of four-week-old Japanese white rabbits. The amount of HA and expression levels of HA synthase (HAS) mRNAs induced by TGF-beta 1 treatment were analyzed by means of high-performance liquid chromatography and real-time polymerase chain-reaction, respectively. Both medium and large amounts of HA were enhanced by the stimulation of TGF-beta 1. HAS2 mRNA expression was enhanced 13-fold after six-hour stimulation with TGF-beta 1 (10 ng/mL), whereas HAS3 mRNA expression was not changed significantly. These results suggest that TGF-beta 1 enhances the expression of HAS2 mRNA in the TMJ synovial membrane fibroblasts and may contribute to the production of high-molecular-weight HA in the joint fluid.

Animals↗
PubMed2004

[Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery].

A five-month-old girl of Down syndrome underwent a corrective surgery for complete atrioventricular septal defect. Her postoperative course was complicated with pulmonary hypertensive (PH) crises despite nitroglycerin (NTG) infusion and inhaled nitric oxide (NO). Sildenafil citrate, a phosphodiesterase 5 inhibitor, was administered through a nasogastric tube at a starting dose of 0.3 mg/kg by stepwise increment to the maximum dose of 2 mg/kg 4 hourly. Sildenafil citrate dramatically lowered pulmonary arterial pressure and the patient was weaned from NTG and NO without PH crisis. There was no side effect after sildenafil citrate administration. Oral sildenafil citrate is a safe and potent adjunct to the existing therapies for postoperative PH in infants after open heart surgery.

Administration, Inhalation↗
PubMed2004

[Beating heart coronary artery bypass grafting for acute myocardial infarction].

We consider that off-pump coronary artery bypass grafting (CABG) [OPCAB], which results in local myocardial ischemia, is more effective for patients with acute myocardial infarction (AMI) than conventional CABG under cardiac arrest with global myocardial ischemia. Twenty-one patients (15 males, 6 females) received OPCAB for AMI, among whom surgery was performed following percutaneous coronary intervention (PCI) failure in 4 and PCI was performed prior to OPCAB in 2, while PCI was not performed in the remaining 15. Preoperatively, 16 patients had intraaortic balloon pumping (IABP), and 4 had IABP and percutaneous cardiopulmonary support (PCPS). The mean interval from onset to surgery was 11.7 (range 3 to 40) hours. In 20 cases, a complete revascularization was performed. The mean number of bypasses was 2.3 and OPCAB was carried out in 14 patients. In 2 cases, OPCAB was converted to on-pump beating CABG for complete revascularization. Fourteen patients (67%), each maintained with preoperative left ventricular ejection fraction (EF), were discharged with an elective bypass. Four patients died after on-pump beating CABG, in whom EF was lower than 10%. In addition, 3 died of low cardiac output syndrome (LOS) under PCPS and 1 of ventricular fibrillation. Based on our results, we considered that complete revascularization using OPCAB was effective for cases of AMI with PCI difficulty. However, in shock cases requiring PCPS, cardiac function was not improved even after revascularization. Therefore, it is necessary to study new procedures for shock cases during the period from onset to surgery.

Aged↗
PubMed2004

[A constrictive pericarditis on oral steroid and immunosuppressant treated with bilateral anterolateral thoracotomy; report of a case].

A successful case of pericardiectomy without median sternotomy for an immunosuppressive 59-year-old man with constrictive pericarditis (CP) was reported. He had a history of invasive thymoma, myasthenia gravis and pure red cell aplasia, and he was on oral steroid and immunosuppressant. Pericardiectomy was performed by the approach of bilateral anterolateral thoracotomy to avoid troubles due to median sternotomy under immunosuppression, and there was no postoperative infection such as mediastinitis. Bilateral anterolateral thoracotomy was considered to be useful for immunosuppressive cases.

Anti-Inflammatory Agents↗
PubMed2003

Mechanical stimuli enhances the expression of RGD-CAP/betaig-h3 in the periodontal ligament.

RGD-CAP, a member of the fasciclin family, is expressed in the periodontal ligament (PDL). Since the PDL is continually subjected to mechanical forces from such orofacial functions as mastication, biting, speech and swallowing, the mechanical stimuli is thought to be associated with the expression of RGD-CAP. Furthermore, the adhesive functions of RGD-CAP may contribute to the maintenance or regeneration of PDL architecture. The objective of this study was to examine whether mechanical stimuli modulate the expression of RGD-CAP in the human PDL, and to examine the effects of recombinant RGD-CAP on the adhesion of PDL cells. During experimental tooth movement, the expression of RGD-CAP was significantly enhanced in the PDL. In vitro experiments with cultured PDL cells showed that the expression of RGD-CAP mRNA was significantly enhanced by mechanical tensile force of 15.4kPa for 48h. The induction of RGD-CAP mRNA, meanwhile, was completely inhibited by cycloheximide which is an inhibitor of protein synthesis. Furthermore, neutralising antibody against TGF-beta also suppressed the mechanical induction of RGD-CAP. The adhesion of cultured PDL cells onto plates coated with recombinant RGD-CAP increased significantly compared with the controls. These findings suggest that RGD-CAP, induced by TGF-beta expressed in response to mechanical stimuli, plays an important role in modulating the homeostasis of PDL.

Blotting, Western↗
PubMed2003

Strong static magnetic field and the induction of mutations through elevated production of reactive oxygen species in Escherichia coli soxR.

PURPOSE: Although strong static magnetic fields (SMF) are supposed to have the potential to affect biological systems, the effects have not been evaluated sufficiently. Experiments should be performed with a powerful SMF-generating apparatus to evaluate the biological effects of SMF. MATERIALS AND METHODS: An Escherichia coli mutation assay was used to assess the mutagenic effects of strong SMF. Various mutant strains of E. coli were exposed to up to 9 Tesla (T) for 24 h and the frequencies of rifampicin-resistant mutations were then determined. The expression of the soxS::lacZ fusion gene was assessed by measurement of beta-galactosidase activity. RESULTS: The results for survival or mutation were obtained with wild-type E. coli strain GC4468 and its derivatives defective in DNA repair enzymes or redox-regulating enzymes were all negative. On the other hand, the mutation frequency was significantly increased by the SMF exposure in soxR and sodAsodB mutants, which are defective in defence mechanisms against oxidative stress. Furthermore, the expression of superoxide-inducible soxS::lacZ fusion gene was stimulated 1.4- and 1.8-fold in E. coli when exposed to 5 and 9 T, respectively. CONCLUSIONS: These results indicate that strong SMF induce mutations through elevated production of intracellular superoxide radicals in E. coli.

Bacterial Proteins↗
PubMed2002

RGD-CAP ((beta)ig-h3) is expressed in precartilage condensation and in prehypertrophic chondrocytes during cartilage development.

RGD-CAP ((beta)ig-h3), isolated from cartilage as a collagen-associated protein, was demonstrated to have a binding ability to collagen and to enhance the adhesion of chondrocytes via integrin alpha(1)beta(1). However, the role of this protein in cartilage development remains unclear. In this study, we investigated the expression of RGD-CAP ((beta)ig-h3) in chick embryos and cultured mesenchymal stem cells (MSCs) during the differentiation to chondrocytes. The effects of recombinant RGD-CAP on adhesion and DNA synthesis of MSCs and mineralization were also examined. Tissue sections from chick embryos at Hamburger-Hamilton (HH) stages 19-37 were immunostained with anti-chick RGD-CAP antibodies. The expression of RGD-CAP was slightest in chick embryos at HH stage 19, whereas a considerable expression of RGD-CAP was observed in the developing vertebrae and precartilage aggregate in the limb bud of chick embryos at HH stage 26. The expression of RGD-CAP was significantly reduced in vertebrae of chick embryo at HH stage 32. Reverse transcriptional polymerase chain reaction (RT-PCR) analysis showed that RGD-CAP was highly expressed in cultured MSCs and decreased by 4-day treatment with 10(-8) M dexamethasone when MSCs proliferated to adipocyte-like cells, whereas it was recovered by co-treatment with 3 ng/ml TGF-beta for 8-12 days when MSCs proliferated to hypertrophic chondrocyte-like cells. The adhesion and DNA synthesis of MSCs cultured on RGD-CAP-coated dishes increased significantly compared with the controls. RGD-CAP was distributed in the prehypertrophic zone in matured cartilage of the vertebrae of chick embryos at HH stage 37. Recombinant RGD-CAP inhibited the mineralization of hypertrophic chondrocytes. These results suggest that RGD-CAP ((beta)ig-h3) exerts an essential role in the early cartilage development by enhancing the adhesion and growth of the pre-chondrogenic cells, and functions as a negative regulator for mineralization at the terminal stage of the chondrogenic differentiation.

Animals↗
PubMed2002

Evidence of oncotic cell death and DNA fragmentation in human hypertrophic chondrocytes in chondro-osteophyte.

OBJECTIVE: To investigate the population and morphology of in situ terminal deoxynucleotidyle transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) stain positive non-apoptotic chondrocytes in hypertrophic zone of human chondro-osteophytes. MATERIALS AND METHODS: Chondro-osteophytes from osteoarthritic patients were obtained at joint replacement surgery. Apoptosis was verified by light microscopic examination of Safranin O stained sections and TUNEL stain. TUNEL staining was also performed on hydrophilic resin embedded semi-thin and ultra-thin sections combined with the treatment with streptavidin-gold conjugates, observed by light microscopy with silver enhancement technique (TUNEL-LM with SE) and transmission electron microscopy (TUNEL-TEM) respectively for the simultaneous evaluation of cellular structure and DNA fragmentation. RESULTS: In paraffin embedded sections (N=18), 31.5+/-6.1% of cells in the hypertrophic zone were TUNEL positive, but only 3.8+/-1.2% cells in this zone showed apoptotic appearances with cell shrinkage and nuclear condensation. Both in TUNEL-TEM and TUNEL-LM with SE, gold particles, which indicate DNA fragmentation, were observed within the nucleus of morphologically apoptotic chondrocytes, as well as of disintegrated, swollen chondrocytes. CONCLUSIONS: In human chondro-osteophytes, hypertrophic chondrocytes might die by oncotic cell death with DNA fragmentation, as well as apoptosis.

Adult↗
PubMed2002

Routine endoscopy using a magnifying endoscope for gastric cancer diagnosis.

BACKGROUND AND STUDY AIMS: It has been reported that the fine mucosal patterns of the gastric pits can be observed with magnification and this may assist in preliminary evaluation prior to histological diagnosis. The aim of this prospective study was to clarify the relationship between the fine mucosal patterns of gastric lesions and histological findings, and also to evaluate the usefulness of magnifying endoscopy during routine endoscopy. PATIENTS AND METHODS: A recently developed magnifying video endoscope, which enables magnification up to 80 times, was used for gastrointestinal endoscopy in 318 patients between January 2000 and January 2001, at the National Shikoku Cancer Center. In total, 232 lesions were detected. However, patients diagnosed by conventional endoscopy as having advanced gastric cancer, malignant lymphoma, or submucosal tumor were excluded from the study. The endoscopic findings for 211 lesions included in this study were compared with the histological findings. RESULTS: Coarse and irregular mucosal patterns were observed in elevated-type cancers by magnifying endoscopy, and in depressed-type cancers there was a finer pit pattern than in the surrounding mucosa, destruction or disappearance of the mucosal microstructure, and abnormal capillary vessels. The magnifying endoscopy results were closely related to the mucosal microstructure observed by dissecting microscopy and to the histological features. The rate of presumptive diagnosis of small gastric cancers was significantly higher when a magnifying endoscope was used compared with conventional endoscopy. In this study, the sensitivity and specificity of magnifying endoscopy as a diagnostic method were 96.0% and 95.5%, respectively. CONCLUSIONS: The fine mucosal patterns and the features of capillary vessels, which were identified with the magnifying endoscope, correlated well with the pathological diagnosis. Magnifying endoscopy will be very useful in predicting the histological diagnosis during routine endoscopic procedures.

Gastric Mucosa↗