Biomedical subjects
Publications and source records attributed to Yosuke Tanaka.
A novel interferometry technique using a frequency-comb light source is proposed for surface profilometry and tomography of discontinuous objects. Surface profile measurement is performed by sweeping the comb interval frequency without mechanical scanning. Step heights of 0.5 and 1.0 mm are successfully measured by use of the scheme with 9 mum accuracy.
The establishment of left-right asymmetry in mammals is a good example of how multiple cell biological processes coordinate in the formation of a basic body plan. The leftward movement of fluid at the ventral node, called nodal flow, is the central process in symmetry breaking on the left-right axis. Nodal flow is autonomously generated by the rotation of cilia that are tilted toward the posterior on cells of the ventral node. These cilia are built by transport via the KIF3 motor complex. How nodal flow is interpreted to create left-right asymmetry has been a matter of debate. Recent evidence suggests that the leftward movement of membrane-sheathed particles, called nodal vesicular parcels (NVPs), may result in the activation of the non-canonical Hedgehog signaling pathway, an asymmetric elevation in intracellular Ca(2+) and changes in gene expression.
A sentinel node biopsy (SNB) has been proved to be an accurate method to estimate the axillary lymph node status as a replacement for axillary lymph node dissection (AxLND) in patients with early breast cancer who have not been treated with neoadjuvant chemotherapy (NAC). We examined the feasibility and accuracy of performing SNB after NAC. Seventy breast cancer patients treated with NAC were enrolled in the current study during the period between March 2001 and June 2005. NAC performed preoperatively consisted of three to four times of CAF chemotherapy. Moreover, intra-arterial (subclavian artery and internal mammary artery) infusion of epirubicin and 5-fluorouracil was performed in addition to systemic CAF chemotherapy once to three times in patients with large breast tumors or bulky axillary lymph node metastases. The sentinel nodes were successfully identified in 63 out of 70 patients (identification rate: 90%). The mean number of sentinel nodes removed per patient was 1.5 (range 1-6). Of the 43 patients in whom AxLND was performed after the sentinel nodes were identified, 19 (44.2%) had positive sentinel nodes. In 8 of those 19 patients, the sentinel node was the only cancer positive lymph node. Among the 24 patients who had negative sentinel nodes it was found that one patient had a confirmed false negative result, thus yielding a false negative rate of 5%, and a sensitivity of 95%. There was no false negative patient who had a clinically negative lymph node status (N0) before NAC (17 patients), whereas the false negative rate was 6.3% in the subgroup of patients with a clinically positive lymph node status (N1, N2) before NAC (26 patients). As a result, SNB after NAC is thus considered to be able to effectively predict the axillary lymph node status in patients with a clinically negative lymph node status before NAC.
A three-dimensional common-path interferometer is proposed, which can achromatically null out an on-axis source while it maintains the detectability of an off-axis source. A geometric phase in the three-dimensional interferometer introduces an achromatic pi-phase shift to the light from the on-axis source, such that destructive interference nulls out the axial light at one of the ports of the interferometer. Light from the off-axis source, which is exempt from the pi-phase shift, comes out from both ports with equal intensity. The common-path scheme makes the system highly immune to environmental disturbances.
The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow.
The precise specification of left-right asymmetry is an essential process for patterning internal organs in vertebrates. In mouse embryonic development, the symmetry-breaking process in left-right determination is initiated by a leftward extraembryonic fluid flow on the surface of the ventral node. However, it is not known whether the signal transduction mechanism of this flow is chemical or mechanical. Here we show that fibroblast growth factor (FGF) signalling triggers secretion of membrane-sheathed objects 0.3-5 microm in diameter termed 'nodal vesicular parcels' (NVPs) that carry Sonic hedgehog and retinoic acid. These NVPs are transported leftward by the fluid flow and eventually fragment close to the left wall of the ventral node. The silencing effects of the FGF-receptor inhibitor SU5402 on NVP secretion and on a downstream rise in Ca2+ were sufficiently reversed by exogenous Sonic hedgehog peptide or retinoic acid, suggesting that FGF-triggered surface accumulation of cargo morphogens may be essential for launching NVPs. Thus, we propose that NVP flow is a new mode of extracellular transport that forms a left-right gradient of morphogens.
In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell-cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of N-cadherin by the KIF3 molecular motor complex is crucial for maintaining this balance. N-cadherin and beta-catenin associate with the KIF3 complex by co-immunoprecipitation, and colocalize with KIF3 in cells. Furthermore, in KAP3-deficient cells, the subcellular localization of N-cadherin was disrupted. Taken together, these results suggest a potential tumour-suppressing activity for this molecular motor.
A 65-year-old male with four-channel aortic dissection successfully underwent replacement of the thoracoabdominal aorta, reconstruction of the celiac, superior mesenteric artery, renal arteries, and 5 pairs of intercostals or lumbar arteries using deep hypothermic technique.
Systemic lupus erythematosus (SLE) is characterized by multisystem inflammation and production of autoantibodies, which can generate immune complexes and may cause tissue damage through the recognition of an autoantigen. Although many factors have been proposed, such as genetic factors, environmental factors, hormonal action, viruses, and dysregulation of cytokine production, the cause of this disease is not well understood. It has been reported that the levels of interferon (IFN)-alpha in the sera of some SLE patients are elevated and that IFN-alpha induces maturation of monocytes into highly active antigen-presenting dendritic cells (DCs). We analyzed the association between IFN-alpha genotype and the risk of SLE to clarify whether IFN-alpha plays a central role in susceptibility to SLE. The results showed that no IFN-alpha genotype was significantly associated with the risk of SLE.
This paper discusses fiber optic power and signal transmission systems considering the application of dc powering to information tools such as personal computers. We discuss system requirements and technical issues for the system components, including high-power laser diodes and photovoltaic cells. It is clarified that the conversion efficiencies of photovoltaic cells are kept constant with heat radiation and improve with extremely small series resistance. The transmittable optical powers through the optical fiber limited by a nonlinear optical effect are estimated. We also discuss the system designs for the use of single- and multi-mode optical fibers.
Our aim was to evaluate the effects of eradication and the incidence of secondary resistance by long-term low-dose daily 14-membered-ring macrolide therapy on Helicobacter pylori ( H. pylori) infection in patients with chronic lower respiratory tract inflammatory disease. In a retrospective analysis, we studied the seroprevalence of H. pylori IgG in 90 patients with inflammation of the lower respiratory tract (68 had been treated with macrolide and 22 served as controls). Then, in a prospective analysis, we evaluated the eradication effect of macrolide therapy by the decline of IgG values and the (13)C-urea breath test. Only long-term macrolide use significantly affected the seroprevalence of H. pylori IgG. However, macrolide therapy did not reduce the H. pylori IgG values in 24 patients and did not eradicate H. pylori in (13)C-urea breath tests. Chemosensitivity testing was performed on three H. pylori strains obtained by gastric biopsy from patients in whom the disease could not be eradicated. Only one strain demonstrated a resistant character. Daily long-term low-dose 14-membered-ring macrolide therapy for patients with lower respiratory inflammatory disease may not be sufficient to eradicate H. pylori, but some strains do not acquire a resistant nature.
We describe a case of hypertrophic cranial pachymeningitis (HCP) associated with Wegener's granulomatosis (WG) in a 60-year-old man presenting with chronic headache and multiple cranial nerve neuropathies. A test for antibodies to the neutrophil cytoplasmic protein myeloperoxidase (MPO-ANCA) was positive in this case. We review the literature on perinuclear (p)-ANCA-related HCP, including our case. This case indicates the link between MPO-ANCA-positive WG and HCP.
Inflammatory bowel disease is an immune-mediated intestinal inflammatory condition that is associated with an increase in autoantibodies that bind to epithelial cells. However, it is unknown whether the epithelial cell-derived products that are recognized by such autoantibodies are involved in the pathogenic process. Through a combined antigen-screening approach utilizing humoral and cellular immune responses, we identify herein an epithelial lectin, galectin-4, that specifically stimulates IL-6 production by CD4(+) T cells. Interestingly, the reactivity of CD4(+) T cells to galectin-4 is precisely elicited under intestinal inflammatory conditions. The galectin-4-mediated production of IL-6 is MHC class II independent and induced by PKCtheta-associated pathway through the immunological synapse. The galectin-4-mediated stimulation of CD4(+) T cells is shown to exacerbate chronic colitis and delay the recovery from acute intestinal injury. These studies identify the presence of an immunogenic, endogenous lectin in the intestine and dissect the biological role of lectin/CD4(+) T cell interactions under inflammatory conditions.
This study was performed to evaluate the utility of initial MRI in predicting the extent of residual disease following neoadjuvant chemotherapy (NAC). The study population consisted of 70 patients with breast cancer (unilateral, n=69; bilateral, n=1) (mean age 51 years) who underwent magnetic resonance imaging (MRI) with gadolinium enhancement both before and after NAC. Basic NAC was comprised of cyclophosphamide, pirarubicin, and 5-fluorouracil. MRI features were compared with pathological diagnosis following surgery. MRI features of breast cancer before NAC were classified as either solitary nodular (SN) (n=33) (47%), or multiple nodular and/or unlocalized dendritic (MN/UD) (n=38) (53%). MRI typing was independent of NAC in 68 tumors (SN, n=32; MN/UD, n=36) (96%, p<0.0001). All except one of the 33 SN tumors (97%) displayed negative margins. In addition, 5 of the 33 SN tumors (15%) displayed pathological complete response (pCR). Conversely, all 5 requiring total glandectomy due to wide infiltration and all except one of the 17 (94%) displaying positive margins necessitating extended resection were classified as MN/UD. Only SN-type tumors on initial MRI have the possibility of pCR after NAC. MN/UD tumors could possess margins necessitating expanded excision or total glandectomy. Morphological concepts based on MRI can prove useful in surgical planning and predicting the extent of residual disease after NAC.
Through interactions with microtubules, the kinesin superfamily of proteins (KIFs) could have multiple roles in neuronal function and development. During neuronal development, postmitotic neurons develop primary axons extending toward targets, while other collateral branches remain short. Although the process of collateral branching is important for correct wiring of the brain, the mechanisms involved are not well understood. In this study, we analyzed kif2a(-/-) mice, whose brains showed multiple phenotypes, including aberrant axonal branching due to overextension of collateral branches. In kif2a(-/-) growth cones, microtubule-depolymerizing activity decreased. Moreover, many individual microtubules showed abnormal behavior at the kif2a(-/-) cell edge. Based on these results, we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension.
A novel profilometry method based on two-photon absorption in a silicon avalanche photodiode is proposed. This method has a wide dynamic range, from millimeters to tens of meters. The principle is experimentally confirmed with a fiber-optic Mach-Zehnder interferometer.
PURPOSE: Penetrating atherosclerotic ulcer (PAU) is an ulceration of an atherosclerotic plaque penetrating through the intima, which may lead to intramural hematoma, aneurysm formation, or rupture. This disease is predominantly found in the thoracic aorta and is uncommon in the infrarenal aorta. The effectiveness of endovascular repair of PAU in the infrarenal aorta was retrospectively investigated. METHODS: From 1999 to 2002, PAU was diagnosed with computed tomography and magnetic resonance imaging in the abdominal aorta in four patients. All patients were men; their average age was 78 years. All four patients had hypertension, and two patients had concomitant coronary artery disease. Three patients had abdominal pain or lumbago. RESULTS: All patients underwent endovascular grafting with a Gianturco Z-stent covered with thin-wall woven Dacron graft. Indications for endovascular intervention were aneurysm formation with or without intramural hematoma in two patients and contained rupture with extraaortic hematoma in two patients. The postoperative course was uneventful in all cases, and no endoleak or aneurysm expansion was recognized during follow-up (4-32 months; average, 14 months). CONCLUSIONS: Infrarenal aortic lesions caused by PAU were generally localized, and endovascular grafting appears to be a feasible alternative to surgical repair.
OBJECTIVE: Of 125 surgical patients with abdominal aortic aneurysm (AAA) treated from 1999, 11 patients with deep shock from ruptured AAAs who underwent aortic occlusion balloon catheter (AOBC) insertion before laparotomy were studied. METHODS: With the patients under local anesthesia, the brachial artery was exposed and the balloon catheter was inserted into the thoracic aorta. The balloon was inflated halfway and pulled back gently to the orifice of the left subclavian artery, and was advanced with the aid of blood flow down to the abdominal aorta. After full inflation of the balloon, the catheter was pulled until the balloon was fixed at the proximal shoulder of the AAA. RESULTS: AOBC insertion was completed within 16.1 +/- 5.1 minutes. Systolic blood pressure at presentation was 84.1 +/- 31.7 mm Hg, deteriorated to 60.9 +/- 15.4 mm Hg on arrival in the operating room, and increased significantly (P <.0001) to 123.4 +/- 25.3 mm Hg after AOBC insertion. The balloon burst in three patients. Embolic complications were observed in two patients. There were three deaths, two associated with the balloon bursting. In nine patients whose shock was successfully controlled by AOBC, operative mortality was 11%. CONCLUSION: Transbrachial arterial insertion of an AOBC may be useful to ameliorate hemorrhagic shock in patients with ruptured AAAs.