Biomedical subjects

Osamu Mikami

Publications and source records attributed to Osamu Mikami.

6 recordsLinked to original sources

PubMed2003

Active optical interconnect based on liquid-crystal grating.

We propose a transparent plate of a liquid-crystal grating to be used as a light guide for optical interconnection. To this end, we are empowering the connection itself with active functions, such as switching, wavelength division, power adjustment, etc. In experiments, we built a grating based on in-plane switching. It contains vertically-aligned nematic liquid-crystal molecules between a glass plate with a high refractive index (light guide) and another glass plate with a pair of interdigitated electrodes. Entering a TM wave from an edge of the light guide, we have demonstrated that the activation of diffraction and intensity adjustment for the guided light are both possible. Because a TE wave is barely diffracted, the device also exhibits polarization division capability.

Journal Article↗

PubMed2003

Hyena disease (premature physeal closure) in calves due to overdose of vitamins A, D3, E.

Holstein suckling calves on a farm manifested severe emaciation, generalized alopecia, dome-like cranial deformation, and high mortality (Case 1). Metaphyseal growth plates of the femur were achondroplastic; segmented, partially resorped, and replaced with immature bony trabeculae containing degenerated chondrocytes. The skull was thin and partially replaced with connective tissue. Diffuse and severe fatty degeneration was observed in the hepatic stellate (Ito') cells. After 6 mo, surviving calves manifested unthrifty with short and irregular hindquarters (Case 2). The metaphyseal growth plates were poorly formed, irregular, partially disappeared centrally, and often sealed with thin bony trabeculae. The cartilage matrix was not homogeneous but was finely fibrous, and chondrocytes were flat and degenerated. The bone lesion was diagnosed as chondrodysplasia due to premature physeal closure. These calves had been administered excessive amounts of vitamins A, D3 and E, and blood chemistry of acute case showed hypervitaminosis A and E. Case I demonstrated acute disease, while Case 2 demonstrated chronic sequelae. Hypervitaminosis A was the suspected cause.

Animals↗

PubMed2003

[Globalization of clinical trials].

Based on reviews of the Japanese clinical trial situation in lung cancer, gastric cancer, prostate cancer and breast cancer, it was clear that much progress has been made in short time. There are considerable differences between Japan and the West and also differences between clinical areas in Japan. For regulatory purposes bridging studies have become increasingly important. Use of identical protocols are required for effective bridging. Participations in global phase III trials is the best way of achieving registration in Japan. For successful global trials in Japan it is important to include Japanese investigators in the preparation of the protocol and to recognise the challenges facing such a project. Clinical practice in diagnosis and treatment have many differences, thus it is recommended to have clear and detailed information in the protocol. Hard end points like survival are important since they are not biased by cultural differences. There are clear difficulties with HE or QOL outcomes. The emergence of focus on evidence based medicine is also happening in Japan and will help to harmonize documentation across the world. For large adjuvant or prevention cancer global trials are essential. To facilitate global studies further development of infrastructure is necessary in Japan. Use of electronic data capture web based communication etc. will help overcome communication difficulties. Other improvements that will make Japanese participation in global trials easier and better include establishment of clinical trial centre at each hospital, introduction of trial coordinators or study nurses and an improved collaboration with company staff. A critical issue that also need addressing is agreement of centre target recruitment. We need to introduce a new flexible system in Japan if participation in global trial is to be optimised. If we can address these issues Japanese investigators and collaborative groups should be able to initiate and lead global trials in the future.

Antineoplastic Agents↗

PubMed2002

Expression of interleukin-18 by porcine airway and intestinal epithelium.

In this study, we investigated the expression of interleukin-18 (IL-18) in porcine airway and intestinal epithelium. We found constitutive protein expression of precursor IL-18 in primary culture of porcine airway epithelium. Immunohistochemical staining revealed that porcine IL-18 was localized in the porcine airway epithelium and that it was significantly upregulated with experimental endotoxemia induced by Escherichia coli lipopolysaccharide (LPS) inoculation. We also confirmed by immunohistochemical staining that IL-18 was expressed in porcine intestinal epithelial cells. Moreover, the concentration of IL-18 in intestinal cell lysates of 1-day-old piglets was about 3-fold and 6-fold less than that in those of 1-month-old and 6-month-old piglets, respectively. Exogenous IL-18 was able to induce interferon-gamma (IFN-gamma) in the peripheral blood of 1-day-old piglets, whereas concanavalin A (ConA) was not able to induce IFN-gamma in the same condition. These results suggest that mucosal epithelial cells are among the major sources of IL-18 in pig and that IL-18 may be useful as a therapeutic agent for the enhancement of immune responses and as a vaccine adjuvant, especially in neonatal piglets.

Age Factors↗

PubMed2002

[Globalization of anti-cancer therapies].

Based on short reviews of lung, gastric, colorectal, prostate, breast and ovarian cancer, there remain significant differences between Japan and the West in the therapeutic regimen for most cancers. Some of the differences are due to differences in stage of disease at diagnosis or historical factors affecting availability of products. In both Japan and the West, there are initiatives to prepare treatment guidelines based on published data. For Japan this initiative is limited by the lack of Japanese clinical trial data or even safety data. When guidelines are prepared from international data, many of the products have limited indications in Japan and therefore not reimbursed. Availability of the most appropriate therapies to Japanese patients will depend on a facilitation of clinical trials in both primary and additional indications. However, the experience in other countries is that, even where data and registration approval are available, guidelines are hard to agree and are not uniformly accepted by prescribers. The ICH E5 guideline on the use of bridging studies to interpolate Western data to Japanese regulatory dossiers provides an opportunity to accelerate availability of new medicines to Japanese prescribers and patients. The use of bridging studies has so far been limited for anti-cancer therapies. Where relevant pharmacodynamic endpoints can be measured, (e.g. aromatase inhibition) there can increase confidence in bridging. The newer types of agent which act to stabilise disease rather than tumour shrinkage present a special problem. In some cases surrogate markers can be valuable but in each case they need to be validated. As globalization continues, an alternative approach is to include a significant cohort of Japanese patients in Japanese patients but this depends on sufficient similarity in the patient population and background therapy. The most significant limitation to either large outcome studies in Japan or for Japanese centers to join international trials has been the environment for conduct of clinical trials. There have been some recent improvements and further progress is expected so that Japanese doctors can play a full role in the evaluation of new therapies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[Post launch studies].

Evidence Based Medicine (EBM) is a growing concept in Japan as it is elsewhere. Central to improving the use of EBM is generation of data through well conducted controlled clinical studies. There are many problems associated with conduct of clinical studies after launch in Japan, and many initiatives are ongoing to improve the situation. Development of Clinical Research Coordinators (CRO) and central Data Management centers are key to improving the quality of clinical research in Japan. Currently Japan has an undeveloped legal system with regard to post-launch trials and off-label use of registered drugs. There is no reimbursement for off-label and various restrictions imposed on the recipients of the Ministry of Health, Labour and Welfare's (MHLW) funds. Maybe the biggest problem is the high cost of post-marketing studies sponsored by pharmaceutical manufacturers. A high quality system to support post launch clinical studies need a solid financial base. There is a need for a suitable review system for investigator initiated multi-centre studies, as the current IRB system is not sufficient. There are also challenges regarding the differences, perceived or real, in treatment practice and available registrations in Japan and in the West, causing problems in choosing suitable comparators and study designs. At the present time it is not clear whether investigator initiated trials will be acceptable for registration purposes in Japan. The agreed first priority is to build a suitable and strong infrastructure within the academic community to support researchers to investigate important questions with or without pharmaceutical company support. Despite all these issues, several groundbreaking projects are under way throughout Japan, in many different areas and by different collaborative groups, some with government support. In fact, researcher-initiated clinical trials achieved a rapid growth in Japan in the past year.

Clinical Trials as Topic↗