After I graduated from Gunma University School of Medicine in 1972, I performed clinical training for a year. Then, I started to work in the field of anatomy in 1973. I received a scholarship from the Alexander von Humboldt Foundation as a research fellow in Medizinische Hochschule Hannover (MHH) from 1977 to 1979. In MHH, I learned a lot about circadian rhythms in the activity of various lysosomal enzymes using histochemical methods and better understood cell dynamism. After returning from Hannover, I started to work on circadian changes in cell organelles including lysosomes of various tissue cells in Tohoku University and the University of Tsukuba. From these studies, I noticed that substantial approaches were required to understand cell dynamism. Then, I started to work on lysosomal proteinases such as cathepsins B, L, and D, and also cell death. From the University of Tsukuba, I also obtained experience in Iwate Medical University, Osaka University Graduate School of Medicine, and Juntendo University Graduate School of Medicine as a professor. In these institutions, I clarified that the gene for cathepsin D is one of the causative genes of neuronal ceroid lipofuscinosis and that autophagic neuron death is present in newborn mouse brains after ischemic-hypoxic injury.

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The author traces his development as a neurosurgeon for 40 years from his formative years of clinical training at Juntendo University and to an experience on his thesis work and basic research at NIH, USA, and ultimately into operative neurosurgery at Juntendo University, East Tokyo Metropolitan and Juntendo University Urayasu Hospitals. It provides a personal perspective of his scientific mind and surgical craft. In this article, the author will attempt to clarify the following five issues. (1) Clinical training with special emphasis of my personal mentorship. (2) Basic research: reappraising the concept of surgeon scientist and of neurosurgery with “scientific mind”. (3) Operative neurosurgery: my special area of interest including skull base surgery, spinal and spine surgery, brainstem surgery, intraorbital tumor surgery, and intraventricular tumor surgery, pediatric epilepsy surgery, and neurovascular decompression. (4) Medical English including the experience of simultaneous translation in medical meetings. (5) Socioeconomic issues: the study on the difference of health care systems between U. S. and Japan.

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I met Professor Lordi n 1978 in Paris, France, and learnedabout Lord-type cementless total hip arthroplasty from him. With this experience as the starting point, I became more interestedin hip surgery and continuedto perform cementless total hip surgery throughout my life. Lord-type cementless total hip prosthesis consists of a screw-in type acetabular component, high-density polyethylene inner socket, cobalt chrome head and a fully porous coated long straight stem. When I returned to Japan in 1979, I startedusing this system in Juntendo University Hospital. From 1979 to 1998, I operated with this system in 228 cases (277 hips). The Kaplan-Meier survival rate (with revision surgery as the endpoint) of the ring acetabular component was 55.1% in 20 years. These revised cases were mostly caused by loosening for mechanical reasons or osteolysis due to polyethylene wear debris. The survival rate of the full porous coatedstem was 92.2% in 20 years. The clinical results of the stem are satisfactory, but those of the screw-in-type acetabular component are poor and it necessitates revision surgery within a short period. Production of the Lord-type total hip system ceasedin 1998, so I subsequently attempted to use many other kinds of prosthesis, such as Omnifit (Stryker), PCA (Howmedica), RMHS, Optiplus (Richards), Profile and S-Rom (DePuy), and now, finally, I use ANCA-FIT (Wright Medical) and CentPillar (Stryker). The number of total hip operations up to March 2013 was 964 hips. Total hip arthroplasty has improvedeach year since the 1960s, in terms of technique, design, andmaterials like cross-linked polyethylene. I hope that the goal of revisionless total hip arthroplasty will be realizedin the future.

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Cervical cancer is caused by infection with human papillomavirus (HPV), discovered by Zur Hausen, a 2008 Nobel laureate in medicine. Regular examination is essential for the prevention of cervical cancer. However, two problems have been pointed out regarding cervical examinationinJapan : low rates of participation in the examination, and the accuracy of cytological diagnoses. If HPV testing is conducted in combination with the cytological diagnoses performed at present, it is estimated that higher levels of screening accuracy will be achieved, and almost 100%of cervical cancer will be detected as a precancerous lesion. Moreover, an HPV vaccine has been developed. The incidence of cervical cancer is expected to decrease to almost zero in the near future because of increased awareness of HPV vaccination and cancer screening including HPV testing.

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I came to Juntendo University directly after graduating from Iwate Medical University in 1975. After finishing a two-year training course, I became a member of the Rheumatology Division at Juntendo University in 1977. Immunology fascinatedme, and my research centered on the regulation of IgE production. I continuedmy research career at Tokyo University (Department of Immunology) from 1978 to 1981 and New York University Medical Center (Department of Pathology) from 1981 to 1983. From 1983 to 1994, I worked as a clinician and researcher at the Rheumatology Division of Juntendo University. I joined the Hematology Division of Juntendo University in 1994, and my research field shifted to transplantation immunology. Juntendo Nerima Hospital was the final destination of my medical career, to which I moved in 2005. At Juntendo Nerima Hospital, I not only worked as a clinician, but also had the pleasure of educating young doctors. Looking back on my 37-year career, Juntendo has taught me the most important fundamentals of human relationships, such as humanity and kindness, through working with colleagues, nurses, and patients.

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In Japan, Trichophyton tonsurans infection has become an increasing problem among participants in martial arts over the last ten years. For the purpose of controlling this infection, a treatment protocol was evaluated. Method : This study involved 6,133 athletes affiliated with judo clubs in the 20 First Division universities that were registered with the University Judo Federation of Tokyo for 5 years. Results : 418 (6.0%) subjects yielded positive hairbrush culture. a. If the number of colonies as observed by the hairbrush method was 2 or fewer, the hair was washed with miconazole shampoo. b. If the number of colonies was 3 or more, 1) itraconazole : 100mg/day for 6 weeks or 400mg/day for 1week, or 2) terbinafine : 125mg/day for 6weeks or 500mg/day for 1week, was administered. 311 (87.1%) of 325 subjects treated with TBF or ITZ were negative;however, the test was not negative in individuals who discontinued the treatment. Conclusion : The pulse-dose regimen was the preferred option in this study. However, there were, in fact, some subjects who were not able to complete the treatment. The following steps are necessary to control infection : 1) determine an effective therapeutic method, 2) set guidelines for disease prevention and control of infection, and 3) establish a network among expert therapeutic institutions to optimize treatment.

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Objective : Preoperative systemic chemotherapy (PSC) has become part of the standard treatment for locally advanced primary breast cancer. The aim of this study was to examine the efficacy of PSC for locally advanced primary breast cancer regarding the association of pathological response with certain biomarkers. Materials : The records of patients treated for breast cancer at Juntendo University Hospital from January 2006 to August 2008 were reviewed from a prospectively collected database. A total of 144 patients diagnosed with primary breast cancer, whose specimens were investigated by immunostaining, underwent PSC during this period. Methods : A comparison was made between the pathological complete response (pCR) and hormonal receptor, human epidermal growth factor receptor type 2 (HER2), Ki-67 and topoisomerase IIα (Topo IIα). The correlations of HER2 with Topo IIα, hormonal receptor and intrinsic subtypes were also studied. Results : pCR was achieved in 16 cases (11%). The rate of pCR was significantly higher in hormonal status-negative cases than in hormonal status-positive ones. pCR in HER2-positive cases, however, showed no significant difference compared with that in negative ones. The rate of pCR was significantly higher in high-Ki-67 cases than in low-Ki-67 ones. pCR showed no significant difference between the high-Topo IIα and low-Topo IIα cases. No correlation was observed in HER2 with Topo IIα and hormonal status. In terms of intrinsic subtype classification, pCR in HER2 type and triple-negative type (i. e. estrogen-negative, progesterone-negative and HER2-negative) was significantly higher in luminal A/ B types. Conclusions : We showed that the efficacy of PSC was affected by not only hormonal-negative and high-Ki-67 status, but also HER2 type and triple-negative type.

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Objective : Cardiac hypoxia-reoxygenation reduces the intracellular magnesium concentration. During hypoxia, an increase in the extracellular magnesium concentration inhibits the decrease in the cardiac intracellular magnesium concentration and protects the heart effectively;however, the underlying mechanisms remain unclear. We hypothesizedthat the influx of ionized magnesium (Mg²⁺) from the extracellular high-Mg²⁺ space into the intracellular space facilitates the recovery of cardiac function. Therefore, we examined the relationship between cardiac function and intracellular magnesium. Materials and Methods : Male Sprague-Dawley rats were sacrificed and the heart of each rat was quickly excisedto establish Langendorff perfusion. After the stabilization period, isoproterenol (iso) was appliedto the hearts, which decreases [Mg²⁺] _i, and was then washedout. After the washout of iso, we examinedthe relationship between cardiac function andcard iac total magnesium content. On the other hand, we studied the [Mg²⁺] _i dynamics under hypoxic conditions with or without transient receptor potential melastatin 7 (TRPM7) inhibitors and under iso-applied conditions using mag-fura2/ AM fluorometry with isolatedrat ventricular myocytes. Results : In the Langendorff perfused rat heart model, the washout of iso resulted in the depression of cardiac function and decrease in the cardiac total magnesium content. Application of iso with a high extracellular Mg2+ concentration improved the recovery of cardiac function and prevented the decline in the cardiac total magnesium content. In isolated cardiac myocytes, [Mg²⁺] _i was only slightly increased by the high extracellular Mg²⁺ concentration under aerobic conditions. However, under hypoxic conditions, a high extracellular Mg²⁺ concentration increased [Mg²⁺] _i substantially. In addition, this increase in [Mg²⁺] _i was suppressedby TRPM7 inhibitors. Conclusions : We demonstrated that a decrease in cardiac total magnesium content due to hypoxia or iso application depresses cardiac contractile function. The depression of cardiac function by the decrease in the cardiac total magnesium content improved because of the high extracellular concentration of Mg2+. This mechanism suggestedthe possibility of an increase in [Mg²⁺] _i by influx from the extracellular high-Mg²⁺ space via TRPM7.

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Objective : The objective of this study was to investigate the usefulness of spectral analysis of frontal lobe EEG using open-eye EEG for determining depressive states. Subjects and Methods : We analyzed the EEG spectra of 22 depressive subjects and 21 control subjects using open-eye EEG. EEG electrodes were placed at Fp1 and Fp2. Subjects were also evaluated by the Self-rating Depression Scale, Social Adaptation Self-evaluation Scale and Gotow Alexithymia Questionnaire. Results : EEG spectrum analysis revealed a significant increase in the S-wave power spectrum in the depressive group. The occurrence of EEG frequency components was characterized by a significant decrease in the alpha band and a significant increase in the delta band in the depressive group. Questionnaire scores also significantly differed between the depressive and control groups, suggesting that the control and depressive groups were validly established. Discussion : In the depressive group, the EEG power spectrum was assumed to increase during activity, similar to the results of other studies for EEG at rest. The occurrence of EEG components differed from previous studies, but showed characteristics of EEG during activity. In addition to an interview with a psychiatrist, there are now a large number of questionnaires and other rating scales devised for the diagnosis of depression and assessment of response to treatment. Objective tests using physiological markers, however, are still under development. The EEG creates a temporal and spatial record of the brain's electrical activity via scalp electrodes to provide an objective evaluation of brain activity. Conventional EEG requires a dedicated EEG room to shield against power source noise, but smaller EEG devices not requiring a shielding space have been developed in recent years, so that EEG can be measured while patients are awake, with their eyes open and performing ordinary activities. The results of this study suggest that spectral analysis of frontal lobe EEG using open-eye EEG could be useful in aiding the diagnosis of depression. These small EEG devices can be used with few environmental restrictions, and as they are non-invasive they are not burdensome for patients. Therefore, further research into their applicability is desirable.

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The 2012 annualworkshop on medical education in Juntendo University (Narita Workshop) took place in Narita on July 20-21, 2012. In total, 182 people attended the workshop, including 103 faculty members, 17 graduates, 26 residents, 23 medical students and 13 administrative staff members. In the workshop, participants were divided into two committees (the medical education committee and the graduate education committee), and they discussed proposals and perspectives on the present status of medical education in the medicalcourse and the graduate course, as well as postgraduate clinical training. The main topic of this workshop was ''New perspectives and proposals on appropriate education in liberal arts, basic science and clinical medicine''. In the workshop on the medicalcourse, the main topic was discussed from the perspectives of liberalarts, basic science, clinical medicine and clinical training, while in the workshop on the graduate course, various proposals were put forward.

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Objective: Adjacent joints including hip joints and knee joints mutually affect each other due to leg length discrepancy and extremity malposition, and severe deformity of these joints may progress. Coxitis knee is the name applied to the particular form of osteoarthritis associated with ankylosis or fixation of the hip joint. Rotational limitations of hip joint and leg length discrepancy cause severe stress to the coxitis knee during walking, resulting in external rotation of the tibia and valgus deformity of the knees, which increase the load on the knee. Materials: In this paper, we describe five cases of total knee arthroplasty performed for severe valgus deformity in patients with ipsilateral coxarthrosis. We investigated the conditions and issues of concern in these patients and report the outcomes. Conclusions: Since the condition of the hip joints is significantly related to valgus knee, it is necessary to carry out comprehensive investigation of the alignment of the legs including not only knee joints but also hip joints. If there is no other option but surgical treatment of the knee joints, then this approach must be prioritized and various efforts must be made.

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We report a case of a 71-year-old man with various symptoms, including appetite loss, sensory disorder of taste, diarrhea and a decrease of body weight. He also presented hepatosplenomegaly, anemia, renal dysfunction and hypoalbuminemia. Although he was diagnosed with systemic amyloidosis through rectal and abdominal fat biopsies, he showed rapidly progressive multiple organ failure, which resulted in death. His autopsy findings contributed to a final diagnosis of primary amyloidosis, caused by monoclonal gammopathy of undetermined significance (MGUS). 1-1.5% of MGUS patients progress to multiple myeloma, amyloidosis, or some other more acute disease within a year. It is important to make a differential diagnosis, including primary amyloidosis, for patients with various symptoms. Even if the patient has a normal level of serum IgG, we need to pay attention to MGUS, as it can progress to multiple organ failure.

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