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Biomedical subjects

Jun Miyazaki

Publications and source records attributed to Jun Miyazaki.

10 recordsLinked to original sources

Determination of a coupling function in multicoupled oscillators.

A new method to determine a coupling function in a phase model is theoretically derived for coupled self-sustained oscillators and applied to Belousov-Zhabotinsky (BZ) oscillators. The synchronous behavior of two coupled BZ reactors is explained extremely well in terms of the coupling function thus obtained. This method is expected to be applicable to weakly coupled multioscillator systems, in which mutual coupling among nearly identical oscillators occurs in a similar manner. The importance of higher-order harmonic terms involved in the coupling function is also discussed.

Journal Article↗

Uroepithelial cells can directly respond to Mycobacterium bovis bacillus Calmette-Guérin through Toll-like receptor signalling.

OBJECTIVE: To investigate, in a human urinary tract cell line, the interaction of Toll-like receptor (TLR) signals with cytoplasmic adapter proteins MyD88 and bacillus Calmette-Guérin (BCG), and evaluate the epithelial cytokine response to BCG infection. Intravesical BCG therapy is effective against carcinoma in situ and as prophylaxis for recurrence, but although immunological mechanisms have been assumed, the mechanisms of the antitumour effects of BCG have not been completely elucidated. MATERIALS AND METHODS: The cell line was first screened for TLR expression by reverse transcription-polymerase chain reaction (RT-PCR). Total RNA was isolated from a human urinary cell line, Hu35E6E7, and cDNA synthesised. PCR was used to measure the gene expression of TLR-2, -3, -4, -5, -9, MyD88, MD-2, CD14 and interleukin-8 and -6. The Hu35E6E7 cell line was cultured in keratinocyte serum-free medium, and BCG was added to the cell culture. After Hu35E6E7 cells were stimulated by BCG for various periods, the total RNA of the cells was extracted. Quantitative real-time PCR was conducted for MyD88 using appropriate probes, and the expression of MyD88 analysed. The cell supernatant was collected, and the levels of interferon-gamma, tumour necrosis factor-alpha, interleukin-2, -12, -4, -6, -10, -8 and -1beta were assayed using an enzyme-linked immunosorbent assay. RESULTS: Uroepithelial cells expressed TLR-2, -3, -4 and -9, and MyD88, MD2, CD14, interleukin-6 and -8 were also detected. At 3, 6, 9 and 12 h after adding BCG, quantitative PCR assay showed that the expression of MyD88 was maximal at 6 h. The presence of BCG stimulated the release only of interleukin-6 and -8 from Hu35E6E7 cells after 6 h. By contrast, interferon-gamma, tumour necrosis factor-alpha, interleukin-2, -12, -4, -10 and -1beta were not detected in the culture supernatant. CONCLUSION: These results show that uroepithelial cells, but not immune cells, responded directly to BCG through TLR signalling. Further investigation is needed to determine the role of cytokines released from uroepithelial cells after BCG infection.

Animals↗

[Renal cell carcinoma with bilateral adrenal and small intestinal metastases: a case report].

A 69-year-old man who had a complaint of melena and hematemesis was referred to our hospital for further evaluation and treatment of renal masses, bilateral adrenal swelling and a tumor in the small intestine. The abdominal CT scan demonstrated two tumors sized 45 mm and 15 mm in diameter, located in the center and lower pole of the left kidney. Bilateral adrenal swelling and a small intestinal tumor with invagination were also observed. We diagnosed left renal cell carcinomas with bilateral adrenal metastases or hyperplasia, and a primary or metastatic small intestinal tumor. He received left radical nephrectomy, right adrenalectomy, and small intestinal resection. Pathological diagnosis was renal cell carcinoma, granular cell carcinoma, G2>G3>G1, INFalpha, v (+), pT1a, pM1, Stage IV. Bilateral adrenal swelling and small intestinal tumor were metastases from the renal cell carcinoma After operation, we administered interferon-alpha and steroid replacement. He died after 27-month follow-up period because of renal cell carcinoma. Renal cell carcinoma with simultaneous metastases to bilateral adrenal glands and the small intestine is extremely rare.

Adrenal Gland Neoplasms↗

Sinus histiocytosis with massive lymphadenopathy associated with malignant lymphoma.

Sinus histiocytosis with massive lymphadenopathy (SHML) is a distinct benign clinicopathological entity, characterized by painless enlargement of lymph nodes due to sinus histiocytosis. Here, we report a case of SHML with diffuse large B-cell lymphoma. A 64-year-old man was admitted to our hospital because of fever. He presented with enlargement of a small cervical lymph node and huge abdominal paraaortic lymphadenopathy. Cervical lymph node biopsy revealed SHML and bone marrow biopsy showed infiltration of large B-cell lymphoma. Several cases of SHML associated with lymphoma have been documented to date, but this type of simultaneous occurrence has not yet been reported.

Histiocytosis, Sinus↗

Paclitaxel, ifosfamide and cisplatin regimen is feasible for Japanese patients with advanced germ cell cancer.

BACKGROUND: Paclitaxel, ifosfamide and cisplatin (TIP) has been tested with successful results on metastatic testicular cancer in Western countries. Because paclitaxel, the key drug of this regimen, has not been approved for testicular cancer in Japan, there are no established data concerning TIP. The purpose of this study was to assess the feasibility of a TIP regimen for Japanese patients with advanced germ cell cancer. METHODS: Eight patients with advanced germ cell cancer were treated with TIP that was originally reported by Motzer et al (1). The treatment was used for three refractory cases and two late relapse cases as salvage therapy and for three poor-risk cases with extra-pulmonary visceral metastases as a part of induction chemotherapy. TIP consisted of paclitaxel 175 mg/m(2) by 24 h infusion on day 1, followed by ifosfamide 1.2 g/m(2) infusions over 2 h and cisplatin 20 mg/m(2 )given over 2 h on days 2-6. RESULTS: Five patients (62%) achieved a disease-free status after chemotherapy and surgical resection of residual tumor. Three of five patients have remained continuously free from disease progression at a median follow-up duration of 24 months and one additional patient is currently free of evidence of disease. Most patients developed grade 3 or 4 leukocytopenia and thrombocytopenia; however, they could be managed with routine supportive care. Sensory neuropathy was frequently seen, but no patient experienced over grade 3 neurotoxicity. CONCLUSIONS: TIP regimen as salvage chemotherapy is feasible for Japanese patients with advanced germ cell cancer. TIP as a part of induction chemotherapy for poor-risk patients is also feasible; however, larger and longer-term follow-up studies are needed to define the role of TIP in this setting.

Adult↗

The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer.

BACKGROUND: Combination chemotherapy of methotrexate, actinomycin D and cisplatin (MAP) is reported to be effective against gestational choriocarcinoma. METHODS: Eight patients with metastatic testicular cancer who had elevated beta-hCG were treated with MAP. They included three refractory cases and two relapsed cases. An additional three patients received MAP as part of the induction therapy. The MAP therapy consisted of methotrexate (10 mg/m2) on days 1-5, actinomycin D (0.01 mg/kg) on days 1-5 and cisplatin (70 mg/m2) on day 1. RESULTS: In all three refractory patients, MAP failed to achieve tumor marker normalization. However, the elevated tumor markers normalized after MAP in the two cases of relapse. Of these two, one patient relapsed again 7 months after MAP and was subsequently salvaged with high-dose chemotherapy. The other patient relapsed and died of the disease 30 months after receiving MAP. Of the three patients who received MAP as part of the induction chemotherapy, one with pure choriocarcinoma achieved tumor marker normalization after MAP and is still alive without disease progression. In the other two patients, MAP failed to achieve marker normalization and the patients received high-dose chemotherapy. The toxicities were mainly bone marrow suppression and mucositis, which were almost acceptable. CONCLUSIONS: The results demonstrated the limited efficacy of MAP as salvage therapy. In addition, the efficacy of MAP as part of induction chemotherapy was negligible. However, there might be some role for MAP as a salvage therapy for patients with pure choriocarcinoma.

Adult↗

[Prevention and management of nephrotoxicity from anti-cancer agents].

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vascular or structures of the kidneys, hemolytic uremic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the prevention and management of anticancer drug-induced renal dysfunction. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to elevation of serum creatinine levels and uremia, electrolyte abnormalities, such as hypomagnesemia and hypokalemia, are well known adverse effects of cisplatin. Methotrexate can cause elevation of serum creatinine levels, uremia and hematuria. Acute renal failure is reported after high dose methotrexate therapy. Urinary alkalization and hydration confer protection against methotrexate-induced renal dysfunction. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome and rickets after ifosfamide administration have been reported in the literature. Hemolytic uremia is a rare but serious adverse effect of gemcitabine.

Antineoplastic Agents↗

Identification of a type III secretion system in uropathogenic Escherichia coli.

To determine virulence-related genes in uropathogenic Escherichia coli (UPEC) showing invasiveness to T-24 bladder cancer cells, genomic subtractive hybridization was performed between a highly invasive and a less invasive strain. Forty-nine DNA fragments were isolated from the invasive strain. One of them showed homology with Salmonella invA gene. By chromosomal walking of the strain, a type III secretion system that has been described in E. coli O157:H7 was identified on the genome of the invasive strains. Three strains out of 100 UPEC isolates had a type III secretion system inserted at 64 min of the chromosome, corresponding to E. coli K-12 MG1655. This finding suggested that the type III secretion system could play a part in uropathogenicity of UPEC.

Bacterial Chromatophores↗

Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells.

Fimbrial (type 1, P, and S) and afimbrial adhesins, the unique virulence traits of uropathogenic Escherichia coli (UPEC), are well recognized for their role in the initial step of uropathogenesis. In this study, we investigated whether these adhesins are dispensable for UPEC in adherence and invasion of uroepithelial cells by using E. coli isolates (n=40) from cystitis patients and T-24 cells, the bladder carcinoma cell line. We found all isolates adherent to T-24 cells within 15 min of infection. In invasion assay, all isolates could invade T-24 cells to a variable degree; 22.5% of them were found highly invasive. About 33% of isolates that do not have any recognized adhesins were as invasive as other isolates. The amplitude of invasiveness was also independent of the adhesins. In conclusion, this study demonstrates that type 1 fimbriae, P fimbriae, S fimbriae, and afimbrial adhesin I are not required for UPEC to adhere to and invade uroepithelial cells.

Adhesins, Escherichia coli↗

Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis.

BACKGROUND: A daily injection of glycyrrhizin (Stronger Neo-Minophagen C (SNMC) containing 40 mg glycyrrhizin in a 20 mL ampoule) lowers alanine aminotransferase (ALT) levels in patients with chronic viral hepatitis. METHODS: The therapeutic effects of intermittent administration of SNMC three times a week for 12 weeks were evaluated and compared between two doses (40 and 100 mL) in a randomized clinical trial. RESULTS: Overall, the therapeutic response was better in the 53 patients allocated 100 mL than the 59 who were allocated to have 40 mL SNMC (P = 0.0243). At the completion of SNMC treatment, ALT levels decreased more extensively in the patients on 100 mL than those on 40 mL SNMC (-29 vs-50% in comparison with the baseline value, P = 0.0002). Minor side-effects occurred in both the patients on 100 mL (20%) and those on 40 mL (12%), but they did not require any therapies. CONCLUSIONS: Intermittent SNMC would be efficient in suppressing ALT levels in patients with chronic viral hepatitis in a dose-dependent manner. Taken along with infrequent and very mild side-effects, long-term intermittent SNMC would benefit patients with chronic hepatitis by maintaining their quality of life with easier compliance.

Alanine Transaminase↗