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Biomedical subjects

Takafumi Yoshida

Publications and source records attributed to Takafumi Yoshida.

At least 19 recordsLinked to original sources
PubMed2007

Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease.

BACKGROUND: Advanced glycation end products (AGEs)-receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non-diabetic healthy subjects. METHODS: Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients. RESULTS: Serum sRAGE levels were significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/- 544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD. CONCLUSIONS: The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non-diabetic subjects and positively associated with the presence of CAD.

Aged↗
PubMed2006

Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation.

There is a growing body of evidence to show that that C-reactive protein (CRP), an acute phase reactant, is one of the most valuable predictors of future cardiovascular events. Since CRP proteins directly contribute to the development and progression of atherosclerosis as well, reduction of CRP levels may be a novel therapeutic target for the treatment of cardiovascular disease. In this study, we examined whether pigment epithelium-derived factor (PEDF) could block the interleukin-6-induced CRP expression in cultured human hepatoma cells and the way that it might achieve this effect. PEDF inhibited the IL-6-induced CRP expression in Hep3B cells at both mRNA and proteins levels. PEDF suppressed the intracellular reactive oxygen species generation in IL-6-exposed Hep3B cells. Anti-oxidants mimicked the effects of PEDF. PEDF was also found to inhibit the IL-6-elicited Rac-1 activation, whereas dominant-negative Rac-1 dose-dependently decreased the CRP mRNA levels. PEDF blocked the IL-6-induced STAT3 phosphorylations and NF-kappaB p65 activity in Hep3B cells. Our present study suggests that PEDF could be one of the potent suppressors of CRP production by the liver and may play a protective role against atherosclerosis.

Antibodies, Monoclonal↗
PubMed2006

Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: an implication for the antitumor potential of flavonoids.

In this study, we have investigated the underlying molecular mechanism for the potent proapoptotic effect of luteolin on human hepatoma cells both in vitro and in vivo, focusing on the signal transducer and activator of transcription 3 (STAT3)/Fas signaling. A clear apoptosis was found in the luteolin-treated HLF hepatoma cells in a time- and dosage-dependent manner. In concert with the caspase-8 activation by luteolin, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr(705) phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was found within 20 minutes in the luteolin-treated cells, leading to down-regulation in the target gene products of STAT3, such as cyclin D1, survivin, Bcl-xL, and vascular endothelial growth factor. Of interest, the rapid down-regulation in STAT3 was consistent with an accelerated ubiquitin-dependent degradation in the Tyr(705)-phosphorylated STAT3, but not the Ser(727)-phosphorylated one, another regulator of STAT3 activity. The expression level of Ser(727)-phosphorylated STAT3 was gradually decreased by the luteolin treatment, followed by a fast and clear down-regulation in the active forms of CDK5, which can phosphorylate STAT3 at Ser(727). An overexpression in STAT3 led to resistance to luteolin, suggesting that STAT3 was a critical target of luteolin. In nude mice with xenografted tumors using HAK-1B hepatoma cells, luteolin significantly inhibited the growth of the tumors in a dosage-dependent manner. These data suggested that luteolin targeted STAT3 through dual pathways-the ubiquitin-dependent degradation in Tyr(705)-phosphorylated STAT3 and the gradual down-regulation in Ser(727)-phosphorylated STAT3 through inactivation of CDK5, thereby triggering apoptosis via up-regulation in Fas/CD95.

Animals↗
PubMed2006

Pigment epithelium-derived factor (PEDF) inhibits advanced glycation end product (AGE)-induced C-reactive protein expression in hepatoma cells by suppressing Rac-1 activation.

Serum levels of advanced glycation end products (AGEs) are associated with an acute phase reactant, C-reactive proteins (CRP) in diabetic patients. However, whether AGEs could directly stimulate hepatic CRP production remains to be elucidated. We found here that AGEs upregulated CRP mRNA levels in cultured Hep3B cells via Rac-1 activation, which was blocked by pigment epithelium-derived factor (PEDF). Our present study suggests that AGEs are one of the potent inducers of CRP and that PEDF may work as an anti-inflammatory agent against AGEs in the liver.

C-Reactive Protein↗
PubMed2006

Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-II-induced vascular endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti-oxidative properties.

Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, elicits numerous inflammatory-proliferative responses, thereby being involved in angiogenesis. T cells play an important role in angiogenesis as well by delivering vascular endothelial growth factor (VEGF) to inflammatory sites. Since we have previously shown that pigment-epithelium-derived factor (PEDF) blocks the Ang II signaling in endothelial cells, we studied here whether PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T and examined the potential mechanism of PEDF inhibitory effects. Ang II significantly up-regulated VEGF mRNA levels in MOLT-3 T cells, which was inhibited by PEDF or olmesartan, an Ang II type 1 receptor blocker. PEDF blocked the Ang-II-induced reactive oxygen species (ROS) generation in MOLT-3 T cells. Furthermore, H(2)O(2) was found to up-regulate VEGF mRNA levels in MOLT-3 T cells in a dose-dependent manner. These results demonstrate that PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T cells via suppression of ROS generation. Blockade by PEDF of VEGF expression in T cells may become a novel therapeutic target for pathological angiogenesis.

Angiotensin II↗
PubMed2006

Fibromatous polyp of the hypopharynx.

We treated a patient with hypopharyngeal fibromatous polyp and speculated the mechanism of this disease. Fibromatous polyp, consisting of fibrous tissue hyperplasia with small vessels, fatty cells and inflammatory cells, is a clinically diagnostic name. Most of pharyngeal fibromatous polyps are arising from the palatine tonsil, and those from the pharyngeal epithelium are rare. The greater part of hypopharyngeal tumors is squamous cell carcinomas, and benign tumors are really uncommon. Fibromatous polyp is not thought to be a true tumor, but the symptoms are almost the same as tumorous diseases, e.g., discomfort in the throat, swallowing difficulty and respiratory distress. Complete resection is used as the treatment method. We operated on this patient under a laryngoscope and successfully resected the polyp. Five months after the operation, there is no sign of recurrence and the patient has no symptoms. This type of polyp is considered to enlarge gradually and it can cause asphyxia and/or dysphagia, so complete ablation should be performed as soon as possible.

Aged↗
PubMed2006

Endothelial progenitor cell transplantation improves the survival following liver injury in mice.

BACKGROUND & AIMS: Neovascularization, which is vital to the healing of injured tissues, recently has been found to include both angiogenesis, which involves in mature endothelial cells, and vasculogenesis, involving endothelial progenitor cells. The aim of this study was to clarify the possible roles of endothelial progenitor cells during postnatal liver regeneration. METHODS: To determine how endothelial progenitor cells participate in liver regeneration, human or mouse endothelial progenitor cells were transplanted into the mice with carbon tetrachloride-induced acute liver injury. Survival rate of the mice in endothelial progenitor cell-transplanted and control groups was calculated. Separately, livers removed temporally from both groups were examined. RESULTS: At an early stage, transplanted human endothelial progenitor cells were seen mainly surrounding hepatic central veins where hepatocytes showed extensive necrosis; later, the transplanted cells formed tubular structures. More of these cells were observed along hepatic sinusoids. Transplantation of human or mouse endothelial progenitor cells improved survival of the mice following liver injury (from 28.6% to 85.7%, P < .0005 and from 33.3% to 80.0%, P < .001, respectively), accompanied by greater proliferation of hepatocytes. Human endothelial progenitor cells produced several growth factors, such as hepatocyte growth factor, transforming growth factor-alpha, heparin-binding epidermal growth factor-like growth factor, and vascular endothelial growth factor, and also elicited endogenous growth factors. CONCLUSIONS: Endogenous and exogenous growth factors and direct neovascularization after endothelial progenitor cell transplantation promoted liver regeneration, thus improving survival after liver injury. Transplantation of endothelial progenitor cells could represent a new therapeutic strategy for promoting liver regeneration.

Animals↗
PubMed2006

Concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate, and leucovorin in patients with advanced resectable squamous cell carcinoma of the larynx and hypopharynx.

CONCLUSIONS: This regimen of concurrent chemoradiotherapy was safe and well tolerated. In terms of larynx preservation, the present regimen appears to be useful for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and hypopharynx. OBJECTIVES: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced resectable SCC of the larynx and hypopharynx, and to demonstrate the feasibility of larynx preservation. PATIENTS AND METHODS: Forty-six eligible patients were treated. The chemotherapy regimen consisted of a combination of four drugs: cisplatin (60 mg/m(2), day 4), 5-fluorouracil (5-FU) (600 mg/m(2) given continuously for 120 h, days 1-5), methotrexate (MTX) (30 mg/m(2), day 1), and leucovorin (LV) (20 mg/m(2), days 1-5). Two cycles of this regimen were given every 4 weeks during radiotherapy. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray, to a total dose of 66.6-70.2 Gray. RESULTS: The 3-year disease-specific survival rates of patients with laryngeal or hypopharyngeal SCC were 81.3% and 78%, respectively. The 3-year disease-specific survival rates with larynx preservation of patients with laryngeal or hypopharyngeal SCC were 46.7% and 59%, respectively. The main toxicities were neutropenia, dermatitis, mucositis, and infection.

Adult↗
PubMed2006

A case of osteochondroma of the atlas causing obstructive sleep apnea syndrome.

Most osteochondromas affect the long bones, but rarely originate in the spine. We report an extremely rare case of osteochondroma of the atlas causing obstructive sleep apnea syndrome (OSAS) in a 61-year-old female. The osteochondroma was removed completely using a transoral approach, and the symptoms of OSAS disappeared. A review of the literature regarding osteochondroma confirms the rarity of this lesion and the use of a transoral approach is discussed.

Body Mass Index↗
PubMed2006

[Change of creatinine clearance rate in accordance with aging in Japanese patients with head and neck cancer].

Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5-fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate pre and post-hydration or combined administration of neutralizing agents is performed during CDDP injection. Before the CDDP administration, we have to evaluate renal function of the patients using creatinine clearance rate (Ccr). In Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over 65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the discrepancy is based on the poor renal function of Japanese. We calculated Ccrs of 107 head and neck cancer patients since January, 2004 to August, 2005, and evaluated renal function before any treatment. Ccr was decreased in proportion to aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65 ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the United States, the average glomerular filtration rate of over 70 year-old healthy people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient kidney function for the administration of CDDP at the dose of 70-100 mg/ m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the United States than in Japan. The incident rate of diabetes, which is the main cause of renal dysfunction, is almost the same in both countries. Though the reason is unclear, it is the fact that the renal function of Japanese decreases quickly in accordance with aging.

Adult↗
PubMed2006

[Clinical efficacy of administration with S-1 alone for head and neck carcinoma].

Most head and neck carcinomas are squamous cell carcinomas (HNSCCs). The combination of cisplatin with a continuous infusion of 5-fluorouracil (5-FU) has been a standard chemotherapy regimen for HNSCC. Based on basic and clinical studies, the critical plasma concentration of 5-FU is suspected to be about 0.1 microg/ml. The administration of the conventional dose of S-1 including dihydropyrimidine dehydrogenase (DPD), an metabolic inhibitor of 5-FU, results in exceeding the critical plasma concentration of 5-FU, and the long-term administration with high plasma concentration of 5-FU is considered to show clinical effectiveness in head and neck cancer. The results of early and late phase II studies on head and neck carcinoma were also described in the present paper.

Administration, Oral↗
PubMed2006

[Adjuvant chemotherapy with S-1 for advanced head and neck carcinoma].

Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant chemotherapy is indispensable for advanced cases with a high relapse risk after standard definitive treatments including surgery and/or radiotherapy. To define an adequate administration schedule in adjuvant chemotherapy with S-1, a controlled randomized study in multi-institutes was done. The results showed the 2-week administration followed by 1-week rest was superior to the 4-week administration followed by the 2-week rest in terms of safety and efficacy. In the present paper, some problems of adjuvant chemotherapy were discussed, and the protocol was described in terms of a multi-institutional controlled randomized comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for locally advanced HNSCC.

Anorexia↗
PubMed2005

A case of metastatic hepatocellular carcinoma in the nasal cavity.

Metastatic hepatocellular carcinoma in the nasal cavity and paranasal sinuses is rare. We report the case of a 71-year-old male afflicted with hepatocellular carcinoma with metastasis in the maxillary sinus and nasal cavity. He underwent radiation therapy with a total dose of 36 Gy, but he died of terminal liver failure. The possible metastatic route and prognosis of metastatic hepatocellular carcinoma in the sinonasal tract are discussed.

Aged↗
PubMed2005

Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components.

Many neurodegenerative diseases are characterized by the presence of protein aggregates bundled with intermediate filaments (IFs) and similar structures, known as Mallory bodies (MBs), are observed in various liver diseases. IFs are anchored at desmosomes and hemidesmosomes, however, interactions with other intercellular junctions have not been determined. We investigated the effect of IF inclusions on junction-associated and cytosolic proteins in various cultured cells. We performed gene transfection of the green fluorescent protein (GFP)-tagged cytokeratin (CK) 18 mutant arg89cys (GFP-CK18 R89C) in cultured cells and observed CK aggregations as well as loss of IF networks. Among various junction-associated proteins, zonula occludens-1 and beta-catenin were colocalized with CK aggregates on immunofluorescent analyses. Similar results were obtained on immunostaining for cytosolic proteins, 14-3-3 zeta protein, glucose-6-phosphate dehydrogenase and DsRed. E-cadherin, a basolateral membrane protein in polarized epithelia, was present on both the apical and basolateral domains in GFP-CK18 R89C-transfected cells. Furthermore, cells containing CK aggregates were significantly larger than GFP-tagged wild type CK18 (GFP-WT CK18)-transfected or non-transfected cells (P < 0.01) and sometimes their morphology was significantly altered. Our data indicate that CK aggregates affect not only cell morphology but also the localization of various cytosolic components, which may affect the cellular function.

14-3-3 Proteins↗
PubMed2005

Four cases of simultaneous triple primary cancers of the hypopharynx, esophagus, and stomach.

OBJECTIVE: To study the efficacy of intensive chemotherapy for simultaneous triple primary cancers of the hypopharynx, esophagus, and stomach. STUDY DESIGN: Retrospective case study. METHODS: From April 2000 to March 2002, we treated 4 patients who had simultaneous triple primary cancers, including hypopharyngeal, esophageal, and gastric carcinomas. These 4 patients were designated as the objects for analysis, and the treatment modality for simultaneous multiple primary cancer cases was examined. RESULTS: In 3 of 4 patients, all 3 primary cancers could be controlled by intensive induction chemotherapy and concurrent chemoradiotherapy for hypopharyngeal cancer and by endoscopic mucosal resection or argon plasma coagulation for esophageal and gastric carcinomas. CONCLUSIONS: In the treatment modality for simultaneous multiple primary cancers, including head and neck cancer, it is important to select intensive systemic chemotherapy and decide the order for treating each primary lesion in consideration of each patient's curability and prognosis.

Aged↗
PubMed2005

A case of metastatic colon adenocarcinoma in the larynx.

Metastatic carcinomas in the larynx are uncommon, and laryngeal tumors originating from the colon are extremely rare. We report a case of metastatic laryngeal tumor originating from a colon adenocarcinoma in an 81-year-old female. Only a tracheostomy was performed because the patient presented with multiple metastases in other regions. The diagnosis, route of metastasis, treatment and prognosis of metastatic laryngeal tumors are discussed.

Adenocarcinoma↗
PubMed2005

Paternal overprotection in obsessive-compulsive disorder and depression with obsessive traits.

Previous studies have indicated that a parental rearing style showing a low level of care on the parental bonding instrument (PBI) is a risk factor for depression, and that there is a relationship between the overprotective rearing style on the PBI and obsessive-compulsive disorder (OCD). However, there is no study on the parental rearing attitudes in depressive patients divided into two groups based on their obsessive traits. In this study, we evaluated the parental rearing attitudes and examined the differences among four groups: depressive patients with severe obsessive traits, depressive patients with mild obsessive traits, OCD patients, and healthy volunteers. We divided the depressive patients into severe and mild groups based on their obsessive traits on the Mausdley Obsessional-Compulsive Inventory (MOCI). We compared PBI scores among four groups of 50 subjects matched for age and sex: depressive patients with severe obsessive traits, depressive patients with mild obsessive traits, OCD patients, and healthy volunteers. The paternal protection scores in the depressive patients with severely obsessive traits and the OCD patients were significantly higher than those in the depressive patients with mildly obsessive traits and healthy volunteers. This study indicated that the depressive patients with severe obsessive traits and the OCD patients have similar paternal controlling and interfering rearing attitudes. We conclude that the paternal controlling and interfering rearing attitudes are linked to the development of OCD and depression with obsessive traits, and are not linked to the development of depression itself.

Adult↗