A group of inspectors, including 28 physicians and 1 student from Fujian Provincial Cancer Hospital, Fujian Medical University Union Hospital, Hospital of Beijing Armed Police Corps etc. visited Juntendo University on August 5, 2014.
First of all, a brief conference was held and Professor Daida and Professor Watanabe gave a short speech of welcome. In the conference, Dr. Nobuko Serizawa gave a talk on gastric cancer chemotherapy in Japan and in Juntendo hospital (Figure-1).
Next, Dr. Jin Kan Sai gave a talk on the diagnosis and treatment of pancreatic cancer in Japan and in Juntendo hospital (Figure-2).
As for the guest speaker from China Yang Jianwei gave a talk about gastric cancer chemotherapy in China including the difference from other countries (Figure-3). During the presentation Dr. Shunsuke Kato gave some comments and questions. Finally, speakers had an active discussion about gastrointestinal cancer.

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Background: Since esophageal carcinoma progresses asymptomatically, for many patients, the disease is already advanced at the time of diagnosis. Compared with other digestive organ cancers, esophageal carcinoma progresses rapidly and has a poor prognosis, making early diagnosis important. There is a need to develop a diagnostic method using clinical markers that is non-invasive while being both highly sensitive and specific.
Method: Exhaled breath was collected from 17 patients with esophageal squamous cell carcinoma, as well as 9 healthy subjects (control group) with no history of cancer. For each fasting subject, 1 L of exhaled breath was collected in a gas sampling bag. Volatile organic compounds (VOCs) were then extracted from each sample using Solid-Phase Micro-Extraction (SPME) fibers and analyzed by gas chromatography.
Results: Comparison of the principal component analyses of the VOCs showed a significant difference between the patient group and the healthy control group. In the patient group, significant increases were observed in 4 VOCs, namely, acetonitrile, acetic acid, acetone, and 2-butanone. Receiver operating characteristic (ROC) curves were drawn for acetonitrile, acetic acid, acetone, and 2-butanone. The calculated area-under-the-curve (AUS) indicated that esophageal carcinoma patients can be identified with a high probability of 0.93.
Conclusions: It was confirmed that there are significant differences in the contents of certain VOCs contained in the exhaled breath of esophageal carcinoma patients compared with that of healthy subjects. The analysis for these VOCs is inexpensive, simple and non-invasive, causing no adverse reactions, and it has potential as a new tool for detecting early-stage esophageal carcinoma.

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Objective: To develop a gait analysis system for children using new algorithms by improving the device that acquires gait data quantitatively.
Background: Quantitative evaluation of child development is essential for early detection and diagnosis of developmental disorders. Gait analysis has been expected to measure and evaluate child development¹⁾. A number of experiments have been undertaken to create a gait analysis system by combining wearable sensors with computational methodologies²⁾. However, these methods are not sufficiently versatile for clinical application. Because the current capabilities of the device and a personal computer (PC) are not sufficient to deal with large data, the methods only provide limited information, such as on joint angle, step length, and gait velocity3). Recently, algorithms using machine-learning schemes have been developed, which can extract patterns from large datasets. In combination with suitable sensor devices, these algorithms could be applied to extract quantitative gait information.
Method: A gait analysis device developed by Hitachi Ltd. for adults was modified for children. This device comprises an inertia sensor to analyze hip joint angles, an insole-type sensor array to measure the center of pressure, and a unit to transmit these gait data to a PC wirelessly. For the safety of children, the device did not feature a hard exoskeleton (stay), although the device for adults used a stay in order to measure knee angle. The device was miniaturized to around 100 grams in weight in order to allow children’s natural movement.
Results: In a trial study on children, the gait analysis device safely acquired the change of hip joint angles and center of pressure in a time series.
Conclusion: Further development of this device and computational methods for gait analysis will facilitate the evaluation of child development.

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Osteoarthritis (OA) of the knee is one of the major causes of locomotive syndrome, defined as being restricted in one’s ability to walk owing to a dysfunction in one or more parts of the motor organs. Although the gait of patients should be measured using motion capture technology, the current devices require a huge space to monitor and scan the patient’s motion, making their use difficult in a clinical setting.
The aim of this study was to introduce novel motion capture technology developed by HITACHI Ltd. to monitor the walking ability of patients with knee OA in a clinical setting. This device consists of linked stays and insole-type pressure sensor arrays. The stays have inertial sensors (accelerometers and gyroscopes) to measure the hip joint angles and potentiometers to measure the knee joint angles. The pressure sensor arrays that are inserted into the shoes measure the balance (center of pressure) of the patients while they walk. This lightweight (350g including shoes) and small (3×5×2cm) device can measure the gait and send the results to a PC. Its accuracy and safety for gait analysis have already been confirmed in comparison to those of conventional motion capture devices.
We measured the gait of patients with end-stage knee OA before and after receiving total knee arthroplasty using this device. We will continue to obtain data about patients with early- to end-stage knee OA after implementation in a clinical setting. We are also planning to examine the association between its pathophysiology and walking ability, and to predict the factors associated with the progression of this disease.

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Finger vein authentication technology has been used for security purposes in banks, public institutions, companies, and other organizations. In this method, near-infrared rays generated from light-emitting diodes (LEDs) penetrate the finger, and are absorbed by the hemoglobin in blood. The veins appear as dark areas on an image captured by a complementary metal oxide semiconductor (CMOS) camera located on the opposite side of the finger¹⁾. We plan to develop a new vascular diagnostic technique using this method to analyze veins in patients with various diseases, such as circulatory diseases.
The device, a U-shaped box, is composed of 850-nm infrared LEDs mounted above and a CMOS camera without an infrared cut-off filter mounted below (Figure-1a, b). The LEDs and CMOS camera are both connected to a personal computer (PC) for power supply, control of the LED brightness, and data processing and storage. When the patient’s finger is placed on the device, the vein patterns are observed as dark lines on the PC display.
It is difficult to measure veins without enhanced angiography, three-dimensional computed tomography, magnetic resonance angiography, or radioisotope venography. Therefore, peripheral venous patterns have not been studied for various diseases. Nevertheless, study of the arteries and veins of the fingers may yield interesting results. Unique venous patterns may be noted in various diseases. Additionally, useful information such as the prognosis of circulatory diseases and early detection of rheumatic diseases may be obtained. Finger vein authentication is noninvasive, and it may be used in a wide range of clinical applications in the future.

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Background: With the increasing incidence of cancer, the number of cases in need of pathological diagnosis has been growing. The number of pathologists is still insufficient, accounting for only about 0.6% of medical doctors in Japan. In addition, accurate diagnosis is an urgent issue in the field of oncology, where the workload in a clinical setting has increased.
In order to facilitate pathological examination, in this study, we developed a new pathological imaging system that screens tissue samples before pathologists test them. Our proposed system is expected to reduce the burden on pathologists, and also to help pathologists to perform more accurate diagnosis of those diseases, especially rare cancers, that need more careful examination.
Methods: Pathological images of clinical samples are produced by shape-of-microscopic-features acquisition equipment in a clinical examination. Our machine learning module, using principal component analysis, neural network, support vector machine, AdaBoost, or random forest, for example, makes it possible to perform pattern matching and to classify a benign or malignant pattern. The pattern recognition classification can determine benignancy or malignancy from pathological images automatically in our proposed pathological image system.
Conclusion: The validity of the developed image recognition algorithm to perform rough classification may currently be slightly controversial. However, the accuracy of the image recognition algorithm will be improved after feedback from clinicians. Future diagnostic imaging systems will enable effective classification of images and have the possibility of being used as educational tools. Our expectation is that this approach can reduce the workload of pathologists. This work has just started, but it should contribute to future diagnosis to determine the pathological type of any malignancy based on the classified images.

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Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. The major clinical features of PD include motor disabilities, such as rigidity, bradykinesia, impaired balance, and resting tremors, as well as non-motor symptoms, such as cognitive decline, psychosis, and autonomic dysfunction. Neuropsychiatric problems seriously affect the activities of daily living and quality of life of PD patients and are caused by a dysfunction not only in dopamine, but also other neurotransmitters, including noradrenaline, serotonin, acetylcholine, and glutamine. Choline esterase inhibitors may improve cognition and visual hallucinations, but not other psychotic symptoms. Although neuroleptics may improve psychiatric problems, these drugs have typically been associated with the deterioration of Parkinsonism. Therefore, the management of hallucinations is an intractable issue for the treatment of PD. Yokukansan, which contains the water extract of a mixture of seven crude drugs, may effectively improve cognition and ameliorate psychiatric problems, such as hallucinations, apathy, and anxiety. We here reviewed yokukansan therapy for and psychiatric problems associated with PD.

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Nocturnal enuresis (NE) is a common problem in children, and its prevalence rate is 20% among children aged 5; 15% of children recover in each subsequent year. However, this problem remains in approximately 0.5% of the adult population. The major pathogenic factors involved in NE are nocturnal polyuria, small bladder capacity and/or detrusor overactivity, as well as a high arousal threshold.
Desmopressin is the first-line medication for patients with dieresis-dependent nocturnal enuresis and its efficacy rate is nearly 70%. An enuresis alarm device is also commonly used, especially for patients with a small bladder capacity; it is effective for 65-70% of patients with NE.
For patients who do not respond to desmopressin or an enuresis alarm, anticholinergics or tricyclic antidepressants are used; however, they are beneficial only for some of them. Since several clinical studies have shown that disrupted sleep architecture in patients with NE might explain in part the etiology of the disease, we evaluated the sleep conditions in our refractory patients and started treatment with yokukansan.
Yokukansan was effective in two-thirds of the refractory cases with nocturnal enuresis by improving the quality of their sleep.

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Yokukansan (YKS) has been used in Japan as a remedy for neurosis, insomnia, and children with night crying. Recently, many studies on the central nervous system (CNS) in terms of the effect of YKS have been reported in Japan. Here, we introduce our studies of YKS effects in the dermatological field. Our first study showed that YKS controls scratching behaviors and inhibits the development of AD-like lesions in isolated NC/Nga mice. In the second study, we compared the efficacy of YKS and fexofenadine (anti-allergic drug) using the same experimental system. Both YKS and fexofenadine inhibit aggravation of AD-like symptoms in socially isolated NC/Nga mice with respect to TEWL and dermatitis scores. However, YKS decreases the scratching and grooming behaviors in socially isolated NC/Nga mice. Thus, we speculate that YKS inhibits the aggravation of AD-like skin lesions in isolated NC/Nga mice due to mechanisms different from fexofenadine. From the results for the central nervous system, we focused on glutamate signaling to evaluate the effect of YKS in the epidermis. Immunohistochemistry and RT-PCR revealed that N-methyl-D-aspartate (NMDA) receptor expression was increased in the skin of conventional control mice and was decreased in YKS-treated mice. Glutamate transporter-1 (GLT-1) mRNA levels were decreased in the skin of conventional control mice and were increased in YKS-treated mice. The results indicate that YKS ameliorates AD-like skin lesions in NC/Nga mice through a mechanism distinct from that of fexofenadine. Our latest experiment showed that the extracellular concentrations of glutamate increased as the cell density increased in cultured keratinocytes. We speculate that this increase originated from an outflow of glutamate from the keratinocytes. Furthermore, the effects of YKS are suggested to regulate epidermal glutamate signaling, notably NMDA receptors, in the epidermis.

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Yokukansan is a formulation containing 15% Uncariae Uncis Cum Ramulus, 10% Bupleuri Radix, 15% Cnidii Rhizoma, 15% Angelicae Radix, 20% Atractylodis Lanceae Rhizoma, 20% Poria and 7% Glycyrrhizae Radix. In addition to its well-established actions on serotonin and glutamate nerve systems, various other effects including suppression of nerve cell excitation, dose-dependent control of brain cell degeneration and protection of nerve sheaths have gradually been elucidated, among which its effectiveness on neuropathic pain has also been evidenced in basic research. In recent years, its wide spectrum of efficacy has given rise to increased use for neuropathic pain along with more conventional applications, such as for treating children’s night cry and symptoms of dementia. Although yokukansan is an easy-to-use formulation, even for elderly patients, care must be taken for the complication of hypokalemia.

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Objective: “Mind reading” is the ability to understand another individual’s mental states. In particular, individuals with developmental disorders, such as autism spectrum disorders, have a deficit in mind reading abilities. Similarly, individual differences in mind reading also exist among the healthy population and are often the cause of misunderstandings. Although the Empathizing and Systemizing Theory (E-S theory) has been used to explain individual developmental differences, its applicability to mind reading among Japanese adolescents has not been investigated. Therefore, the purpose of this study was to examine whether the E-S theory explains individual differences in mind reading among Japanese adolescents.
Participants: Participants were 240 Japanese university students (M=20.58, SD=0.51).
Methods: We administered questionnaires based on Japanese versions of the Empathy and Systemizing Quotients, and the Reading the Mind in the Eyes Test.
Results: Empathizing, but not systemizing, was found to be related to mind reading. Additionally, relative differences in empathizing and systemizing, rather than its combination, were associated with mind reading.
Conclusion: Since relative differences in empathizing and systemizing affect mind reading, we concluded that the E-S theory explains individual differences in mind reading among Japanese adolescents.

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Objective: The single nucleotide polymorphisms (SNPs) close to the IL28B gene are strong predictors of response to interferon-based therapy for chronic hepatitis C patients. However, approximately 20% of patients have discordant responses to the therapy, suggesting that undiscovered variants of the SNPs may be present near to this disease-associated gene. We sought to develop a practical approach to explore rare variants involved in the treatment response, based on next-generation sequencing (NGS) technology.
Materials: Eight patients with the favorable genotype of the IL28B SNP (TT of rs8099917) who underwent 48 week of pegylated interferon-α and ribavirin therapy were enrolled in the study. They were categorized in two groups according to their virological response, 5 achieved an early virological response (EVR) while the others had a null virological response (NVR).
Methods: PCR primers were developed to amplify specifically IL28B and the relevant IL28A genes. The amplicons were sequenced by an NGS and capillary sequencing was used to validate the variations identified by NGS.
Measurements and Results: Target regions around IL28B and IL28A were specifically amplified by the in house primer sets. Real-time PCR was introduced to control the number of sequence reads on each sample before NGS analysis. Four candidate rare variants were identified through comparative NGS analyses of the EVR and NVR groups. In order to validate the results of the NGS, we subsequently used capillary sequencing but failed to confirm the existence of these rare variants.
Conclusions: We have established a technical serial sequencing platform with NGS, potentially enabling the discovery of rare variant SNPs in genes of interest, such as IL28B in HCV infection.

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In this review, I would like to discuss the effects of ionizing radiation on human beings, and protection against it. X-rays or γ-rays are electromagnetic radiation with short wavelengths, and have sufficient energy to cause the ejection of one or more orbital electrons from an atom or molecule. This process is called ionization, and this kind of radiation is referred to as ionizing radiation. There are other high-energy particles that have an ionizing effect, and they are all regarded as ionizing radiation. Ionizing radiation can be artificially made, or originate from radioisotopes or space.
Ionizing radiation can cause cell death or genomic mutation, which is related to carcinogenesis. Only ionizing radiation over the threshold dose can cause symptoms related to cell death (deterministic effects), whereas we suppose that there is no threshold for carcinogenesis (stochastic effects) by radiation in terms of safety. A dose limitation has been established for occupational and public exposure, with the aim of preventing deterministic effects and reducing risks of stochastic effects to the extent reasonably achievable. Radiation therapy is one of the most useful treatment modalities for cancers. Currently, we can use many modern treatment modalities in radiation therapy in addition to standard external-beam therapy.

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Glucosamine, a naturally occurring amino monosaccharide, is present in the connective and cartilage tissues as a component of glycosaminoglycans. Thus, glucosamine has been widely used to treat osteoarthritis, a joint disease characterized by cartilage degeneration, in humans. We previously revealed that glucosamine induces the production of hyaluronic acid by synovial cells and chondrocytes, and increases the expression of hyaluronic acid-synthesizing enzymes (HAS) in these cells, indicating that it exhibits chondroprotective action on osteoarthritis by modulating the expression of HAS and inducing the production of hyaluronic acid (a major component of glycosaminoglycans) by synovial cells and chondrocytes. Furthermore, we recently examined the expression of the sirtuin (SIRT) gene family in chondrocytes, and revealed that glucosamine significantly increased the mRNA and protein levels of SIRT1 (a putative gene involved in lifespan elongation) in chondrocytes, suggesting that glucosamine can upregulate the mRNA and protein levels of SIRT1 in chondrocytes, thereby possibly exhibiting protective action against osteoarthritis.
In addition, glucosamine is expected to exert anti-inflammatory action since it downregulates the expression of pro-inflammatory cytokines. We recently identified a transcription factor, Sp1, as an O-linked-N-acetylglucosamine (O-GlcNAc) -modified protein. Namely, glucosamine enhanced the O-GlcNAc modification of Sp1, and the effect was abolished by alloxan, an O-GlcNAc transferase inhibitor. Moreover, glucosamine downregulated the expression of IL-8, and the effect was abrogated by alloxan. These observations apparently suggest that glucosamine modulates (suppresses) IL-8 expression via the O-GlcNAc modification of Sp1 in synovial cells.
Together, these observations indicate that glucosamine can be therapeutically utilized as a functional molecule with chondroprotective and anti-inflammatory actions in the body.

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