Maya Sakamoto

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

WE used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

Accuracy of intraoral radiography, multidetector helical CT, and limited cone-beam CT for the detection of horizontal tooth root fracture.

OBJECTIVE The accuracies of intraoral radiography (IOR), multidetector helical computerized tomography (MDHCT) at slice thicknesses 0.63 mm and 1.25 mm, and limited cone-beam computerized tomography (LCBCT) were compared for detection of horizontal tooth root fracture. STUDY DESIGN In 7 beagle dogs, 28 maxillary anterior teeth were used, of which 13 had artificially induced horizontal root fracture. The specimens were examined by the above-mentioned 4 modalities. Diagnosis of root fracture was based on direct visualization of radiolucent line in each image by 6 radiologists. RESULTS Sensitivity, negative predictive value, and diagnostic accuracy (true positives + true negatives) for detecting fracture lines in LCBCT (0.96 +/- 0.04, 0.97 +/- 0.03, 0.93 +/- 0.04, respectively) were significantly higher than MDHCT at 0.63 mm (0.76 +/- 0.09, 0.8 +/- 0.05, 0.8 +/- 0.05, respectively), MDHCT at 1.25 mm (0.49 +/- 0.09, 0.66 +/- 0.04, 0.69 +/- 0.05, respectively), and IOR (0.51 +/- 0.18, 0.67 +/- 0.08, 0.69 +/- 0.08, respectively). Specificity and positive predictive value showed no significant intermethod difference among the 4 modalities. CONCLUSION Limited cone-beam CT is more useful than the other 3 radiographic modalities for diagnostic imaging of horizontal tooth root fracture.

Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light

Lymph node dissection for regional nodal metastasis is a primary option, but is invasive and associated with adverse effects. The development of non-invasive therapeutic methods in preclinical experiments using mice has been restricted by the small lymph node size and the limited techniques available for non-invasive monitoring of lymph node metastasis. Here, we show that photothermal therapy (PTT) using gold nanorods (GNRs) and near-infrared (NIR) laser light shows potential as a non-invasive treatment for tumors in the proper axillary lymph nodes (proper-ALNs) of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes (up to 13mm in diameter, similar in size to human lymph nodes). Tumor cells were inoculated into the proper-ALNs to develop a model of metastatic lesions, and any anti-tumor effects of therapy were assessed. We found that GNRs accumulated in the tumor in the proper-ALNs 24h after tail vein injection, and that irradiation with NIR laser light elevated tumor temperature. Furthermore, combining local or systemic delivery of GNRs with NIR irradiation suppressed tumor growth more than irradiation alone. We propose that PTT with GNRs and NIR laser light can serve as a new therapeutic method for lymph node metastasis, as an alternative to lymph node dissection.

Mouse model of lymph node metastasis via afferent lymphatic vessels for development of imaging modalities.

Animal studies of lymph node metastasis are constrained by limitations in the techniques available for noninvasive monitoring of the progression of lymph node metastasis, as well as difficulties in the establishment of appropriate animal models. To overcome these challenges, this study has developed a mouse model of inter-lymph-node metastasis via afferent lymphatic vessels for use in the development of imaging modalities. We used 14- to 18-week-old MRL/MpJ−/lpr/lpr (MRL/lpr) mice exhibiting remarkable systemic lymphadenopathy, with proper axillary lymph nodes (proper-ALNs) and subiliac lymph nodes (SiLNs) that are 6 to 12 mm in diameter (similar in size to human lymph nodes). When KM-Luc/GFP malignant fibrous histiocytoma-like cells stably expressing the firefly luciferase gene were injected into the SiLN, metastasis could be detected in the proper-ALN within 3 to 9 days, using in vivo bioluminescence imaging. The metastasis route was found to be via the efferent lymphatic vessels of the SiLN, and metastasis incidence depended on the number of cells injected, the injection duration and the SiLN volume. Three-dimensional contrast-enhanced high-frequency ultrasound imaging showed that the blood vessel volume and density in the metastasized proper-ALN significantly increased at 14 days after tumor cell inoculation into the SiLN. The present metastasis model, with lymph nodes similar in size to those of humans, has potential use in the development of ultrasound imaging with high-precision and high-sensitivity as well as other imaging modalities for the detection of blood vessels in lymph nodes during the progression of metastasis.

Volumetric and Angiogenic Evaluation of Antitumor Effects with Acoustic Liposome and High-Frequency Ultrasound

Acoustic liposomes (AL) have their inherent echogenicity and can add functionality in serving as drug carriers with tissue specificity. Nonuniform vascular structures and vascular branches/bends are evaluated by imaging the intravascular movement locus of ALs with high-frequency ultrasound (HF-US) imaging. However, the evaluation of antitumor effects on angiogenesis by ALs and HF-US imaging has not been reported. Here, we show that the combination of ALs and an HF-US imaging system is capable of noninvasively evaluating antitumor volumetric and angiogenic effects in preclinical mouse models of various cancers. In this study, the antitumor effects of cisplatin on tumor growth and angiogenesis in mice bearing two different types of tumor cells were assessed. By tracking each AL flowing in the vessel and transferring the images to personal computers, microvessel structures were mapped and reconstructed using the color difference based on SD method. The antitumor effects were confirmed with an in vivo bioluminescence imaging system and immunohistochemical analysis. Our results show that cisplatin inhibits tumor growth by decreasing intratumoral vessel area but does not affect the angiogenesis ratio in the tumor. The vascular occupancy in the outer region of the tumor was larger than that in the inner region; however, both occupancies were similar to those of the control tumor. We propose that this method of mapping microvessels with ALs and an HF-US system can serve as a new molecular imaging method for the assessment of angiogenesis and can be applied to evaluate the antitumor effects by various therapeutic agents.

Detection of ABCA7-positive cells in salivary glands from patients with Sjögren's syndrome

ABCA7 is a member of the subfamily A of adenosine triphosphate‐binding cassette (ABC) proteins, and highly homologous to ABCA1, which mediates the release of cellular cholesterol and phospholipid to form high‐density lipoprotein. ABCA1 and ABCA7 contain two large extracellular domains, ECD1 and 2, which are thought to be important for their functions. Interestingly, part of ECD1 of ABCA7 is deposited as an autoantigen of Sjögrens syndrome. To determine the relationship between ABCA7 and Sjögrens syndrome, an immunohistochemical study was conducted with salivary gland biopsy samples from patients with Sjögrens syndrome. ECD1 of human ABCA7 (amino acids 45–549) was expressed in Escherichia coli as a protein fused with glutathione‐S‐transferase and a monoclonal antibody, KM3095, was generated. KM3095‐immunoreactive cells were observed in salivary glands from 10 of 18 patients with Sjögrens syndrome. Immunostaining of serial sections with the plasma cell marker NCL‐PC indicated that most of the plasma cells infiltrating salivary glands of patients with Sjögrens syndrome were KM3095‐immunoreactive. Although the pathological or biological significance is not clear, it will be intriguing to further examine the relationship between ABCA7 and Sjögrens syndrome.

Delivery of Molecules to the Lymph Node via Lymphatic Vessels Using Ultrasound and Nano/Microbubbles

Lymph node (LN) dissection is the primary option for head and neck cancer when imaging modalities and biopsy confirm metastasis to the sentinel LN. However, there are no effective alternative treatments to dissection for LN metastasis. Here, we describe a novel drug delivery system combining nano/microbubbles (NMBs) with ultrasound (US) that exhibits considerable potential for the delivery of exogenous molecules into LNs through the lymphatic vessels. A solution containing fluorophores (as a model of a therapeutic molecule) and NMBs was injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs (up to 13 mm in diameter, similar to human LNs). It was found that the NMBs were delivered to the entire area of the proper axillary LN (proper-ALN) via the lymphatic channels and that these were retained there for more than 8 min. Furthermore, exposure to US in the presence of NMBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared with exposure to US in the absence of NMBs. It is proposed that a system using US and NMBs to deliver therapeutic drugs via lymphatic vessels can serve as a new treatment method for LN metastasis.

Direct Delivery of a Cytotoxic Anticancer Agent into the Metastatic Lymph Node Using Nano/Microbubbles and Ultrasound

Direct injection of an anticancer agent into a metastatic lymph node (LN) has not been used as a standard treatment because evidence concerning the efficacy of local administration of a drug into a metastatic LN has not been established. Here we show that the combination of intralymphatic drug delivery with nano/microbubbles (NMBs) and ultrasound has the potential to improve the chemotherapeutic effect. We delivered cis-diamminedichloroplatinum (II) (CDDP) into breast carcinoma cells in vitro and found that apoptotic processes were involved in the antitumor action. Next, we investigated the antitumor effect of intralymphatic chemotherapy with NMBs and ultrasound in an experimental model of LN metastasis using MXH10/Mo-lpr/lpr mice exhibiting lymphadenopathy. The combination of intralymphatic chemotherapy with NMBs and ultrasound has the potential to improve the delivery of CDDP into target LNs without damage to the surrounding normal tissues. The present study indicates that intralymphatic drug delivery with NMBs and ultrasound will potentially be of great benefit in the clinical setting.

Important Role of Umami Taste Sensitivity in Oral and Overall Health

Our newly developed umami taste sensitivity test revealed the loss of only the umami taste sensation in some elderly patients, whereas the other four basic taste sensations (sweet, salty, sour, bitter) were normal. Such patients all complained of appetite loss and weight loss, resulting in poor overall health. As a treatment for taste disorder patients, improvement of salivary flow has been adopted in our clinic. Umami taste stimulation increases salivary flow rate of not only major but also minor salivary glands. After treatment with umami taste stimulation, patients remarkably regained their appetite, weight and overall health. Sensitivity to umami taste seems to contribute to good overall health in elderly people.

A simple, yet accurate method for detecting and quantifying secretions from human minor salivary glands using the iodine-starch reaction.

The lack of published information about the minor salivary glands is due in part to the difficulties experienced in collecting and quantifying their secretions. In fact, no method exists for measuring their secretions that is both simple and accurate. This investigation examined the accuracy of our newly developed method (which simply employs the iodine-starch reaction) in 10 healthy non-medicated adults. A strip painted with a solution of iodine in absolute alcohol then with a fine starch powder mixed with castor oil was placed at a designated location on the lower-lip mucosa for 2 min to collect saliva. Black-stained spots of various sizes corresponding to the individual glands could be accurately visualized. After removal of the strip, the total stained area (mm2) was calculated by digitizing the spot areas using a computer system. The correlation coefficient (r) between known volumes of saliva and stain size was 0.995, indicating a close correlation. The correlation coefficient (r) between area values obtained in the first trial in each subject (Y) and the second (X; 10 min later) was 0.963, and the simple regression equation was close to Y=X, indicating good reproducibility. The mean flow rate microl/cm2 per min) obtained by converting mean total area to volume and thence to flow rate was 0.49+/-0.26, in good agreement with published values obtained by others. These results suggest that our newly developed method allows both the distribution and secretion rate of the minor salivary glands to be observed, and that it should be of practical value due to its simplicity, accuracy, and reproducibility.