-
[show abstract]
[hide abstract]
ABSTRACT: Lidocaine is a local anesthetic that is known to suppress tinnitus via systemic or local application; however, this effect has only limited duration. The current study aimed to establish a method for the sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid (PLGA) microparticles.
Experimental study.
Lidocaine-loaded PLGA microparticles were produced and their in vitro-release profiles were examined. The lidocaine concentrations in the perilymph were measured at different time points following the application of the lidocaine-loaded PLGA microparticles to the round-window membranes of guinea pigs. The possible adverse effects of the local application of lidocaine-loaded PLGA microparticles were also examined.
The in vitro analyses revealed that the microparticles were capable of the sustained delivery of lidocaine. The in vivo experiments demonstrated the sustained delivery of lidocaine into the cochlear fluid, and the maintenance of high lidocaine concentrations in the perilymph for up to 3 days after application. Nystagmus and inflammation in the middle ear mucosa were not detected after the local application of lidocaine-loaded PLGA microparticles, although temporary hearing loss was observed.
Lidocaine-loaded PLGA microparticles were shown to be capable of the sustained delivery of lidocaine into the cochlea, suggesting that they could be used for the attenuation of peripheral tinnitus.
The Laryngoscope 11/2009; 120(2):377-83. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: DOCK180 is a guanine exchange factor of Rac1 originally identified as a protein bound to an SH3 domain of the Crk adaptor protein. DOCK180 induces tyrosine phosphorylation of p130(Cas), and recruits the Crk-p130(Cas) complex to focal adhesions. To understand the role of DOCK180 in cell adhesion and migration, we searched for DOCK180-binding proteins with a nano-LC/MS/MS system, and identified ANKRD28, a protein that contains twenty-six ankyrin domain repeats. Knockdown of ANKRD28 by RNA interference reduced the velocity of migration of HeLa cells, suggesting that this protein plays a physiologic role in the DOCK180-Rac1 signaling pathway. Furthermore, knockdown of ANKRD28 was found to alter the distribution of focal adhesion proteins such as Crk, paxillin, and p130(Cas). On the other hand, expression of ANKRD28, p130(Cas), Crk, and DOCK180 induced hyper-phosphorylation of p130(Cas), and impaired detachment of the cell membrane during migration. Consequently, cells expressing ANKRD28 exhibited multiple long cellular processes. ANKRD28 associated with DOCK180 in an SH3-dependent manner and competed with ELMO, another protein bound to the SH3 domain of DOCK180. In striking contrast to ANKRD28, overexpression of ELMO induced extensive lamellipodial protrusion around the entire circumference. These data suggest that ANKRD28 specifies the localization and the activity of the DOCK180-Rac1 pathway.
Experimental Cell Research 01/2009; 315(5):863-76. · 3.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H(2)O(2), which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5'-triphosphate and guanosine 5'-triphosphate, did not inhibit this reaction. Second, we used time-lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT-5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8-hydroxy-2'-deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron.
Cancer Science 10/2008; 99(11):2142-51. · 3.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to elucidate the embryologic basis of fused umbilical arteries in the human.
Twenty-nine human embryo specimens at Carnegie stages 11 through 15 (4-5 weeks after fertilization) were examined histologically, with special reference to the development of umbilical arteries.
All embryos at Carnegie stage 11 and 12 had fused umbilical arteries, and 66% of Carnegie stage 13 embryos and 29% of Carnegie stage 14 embryos still had the condition. None of the embryos at Carnegie stage 15 or older had fused umbilical arteries, but there were always 2 arteries present in their umbilical cords.
Our data suggest that (1) a single umbilical artery splits into 2 as the developmental stage of the embryo advances, (2) that fused umbilical arteries represent a remnant of the embryonic phenotype, and (3) that fused umbilical arteries are embryologically distinct from true single umbilical artery.
American journal of obstetrics and gynecology 12/2005; 193(5):1709-15. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The authors describe a case of posttransplant lymphoproliferative disorder (PTLD) in a 38-year-old Japanese male patient who had undergone bilateral lung transplantation. Chest CT performed on day 109 revealed multiple lung nodules measuring approximately 1cm in the left lower lobe. Despite administration of anti-fungal agents, follow-up CT performed on day 138 showed bilateral lung nodules increased in size and number. Transcutaneous lung biopsy was performed, yielding a diagnosis of polymorphic PTLD positive for Epstein-Barr virus (EBV)-encoded RNA (EBER) and CD20. Treatment with rituximab was successful, resulting in decreased size and number of lung nodules. FDG-PET showed no increased metabolic activity in the residual nodules. In this case, CT and FDG-PET were useful for initial diagnosis and evaluation of treatment response. To the best of our knowledge, this is the first report of PTLD in a lung transplant recipient in Japan documented in the English literature.
Journal of Thoracic Imaging 12/2005; 20(4):280-3. · 0.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 73-year-old man presented with an ulcer and a subcutaneous nodule where he was receiving leuprorelin acetate injections to treat his prostatic carcinoma. Pathological findings of a skin biopsy showed many epithelioid granulomas with multinuclear giant cells, which contained small vacuoles. Recently, these lesions have been suggested to be caused by a type IV allergic response to the copolymer of lactic and glycolic acids used as a vehicle for drug administration. When urologists treat a prostatic adenocarcinoma with subcutaneous infusion of leuprorelin acetate, they should be aware of this potential side effect of the drug because the resulting granulomar formation may interfere with the effect of the drug. If patients suffer from subcutaneous nodules, urologists should consider changing the drug to an other type of luteinizing hormone-releasing hormone analogues such as goserelin acetate. This reaction to leuprorelin acetate has been reported in only seven cases including our case.
Hinyokika kiyo. Acta urologica Japonica 04/2004; 50(3):199-202.
-
[show abstract]
[hide abstract]
ABSTRACT: We report a case in which a living related renal transplantation was successfully performed for end-stage renal disease that had progressed after a liver transplantation from a brain-dead donor for liver cirrhosis associated with type C hepatitis. Because the transplanted liver function had been excellent with the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents with prednisolone were employed for the renal transplantation. Both grafts are functioning well without recurrence of hepatitis at 10 months after the renal transplantation. From our experience, renal transplantation should not be contraindicated even if the patient has undergone liver transplantation or has hepatitis C viral infection.
International Journal of Urology 12/2003; 10(11):607-9. · 1.75 Impact Factor
-
Eijiro Nakamura,
Yuzuru Megumi,
Takashi Kobayashi,
Toshiyuki Kamoto,
Satoshi Ishitoya,
Toshiro Terachi, Mitsuhiro Tachibana,
Hisanori Matsushiro,
Tomonori Habuchi,
Yoshiyuki Kakehi,
Osamu Ogawa
[show abstract]
[hide abstract]
ABSTRACT: It has been suggested that the immune system of the host may be capable of modulating the clinical course of renal cell carcinoma (RCC) patients. In fact, the amount of Th2 cytokines such as interleukin (IL)-4 and IL-10 in the serum of patients has been found to be an important predictor of poor prognosis. Recently, it was reported that genetic polymorphisms of the IL-4 receptor alpha (IL-4Ralpha) gene affect the strength of signaling through the receptor. In addition, these same polymorphisms were found to be associated with an increased risk of atopy by causing Th2-dominated responses of the host. The significance of the polymorphisms on the incidence and prognosis in sporadic RCC patients were examined to clarify the role of IL-4 as well as that of the Th1/Th2 immune system in this disease.
A case-control study was performed with 143 sporadic RCCs in a Japanese population and 205 Japanese controls. Logistic regression models were also used to assess the genetic effects on prognosis.
The frequencies of variant alleles that enhance signaling of IL-4 were significantly related to an increased risk of RCC. Furthermore, multivariate regression analysis showed that the genotype of the IL-4R gene was an independent prognostic factor for cause-specific survival (P = 0.018) together with M classification (P = 0.0002) and histopathological grade (P = 0.044).
The present findings show that the preferential Th2-type response to tumors was associated with a poorer prognosis and suggest that polymorphisms of the IL-4Ralpha gene may serve as useful genetic markers for assessing the risk of the development and progression of RCC.
Clinical Cancer Research 09/2002; 8(8):2620-5. · 7.74 Impact Factor
-
Mitsuhiro Tachibana
[show abstract]
[hide abstract]
ABSTRACT: Kyoto University (京都大学) 0048 新制・課程博士 博士(医学) 甲第14480号 医博第3325号 新制/医/973 UT51-2009-D192 2009-03-23 京都大学大学院医学研究科内科系専攻 (主査)教授 成宮 周, 教授 玉木 敬二, 教授 芹川 忠夫 学位規則第4条第1項該当
