A group including 8 physicians and 6 nurses from Mahidol University visited Juntendo Tokyo Koto Geriatric Medical Center (GMC) on July 11, 2014. First of all, a brief conference was held and the president of the center, Dr. Hiroshi Tsuda, gave a welcoming speech. In the conference, Dr. Yoshiaki Furukawa gave a talk on the clinical characteristics of the GMC (Table-1) ¹⁾ and Dr. Yosuke Ichimiya gave a short lecture on the diagnosis and treatment of demented patients at this center (Figure-1) as well as the activities of the GMC psychiatric team (Table-2) ^{2) -4)}. Then, the visitors observed general and psychiatric wards, rooms for medical examinations of outpatients, and rehabilitation rooms in the center. Finally, Dr. Somnuek Domrongkitchaiporn expressed his gratitude and gave a talk about how aging of the population is progressing in Thailand (Figure-2).

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Ongoing climate change in recent years has produced higher temperatures and has increased the number of extremely hot days in many parts of the world. With this climate change, casualties due to heat disorders have also tended to increase in the workplace as well as the local community in Japan. To cope with this urgent occupational and environmental health problem, the Japanese government has been forced to take prompt preventive measures against heat disorders.
This paper firstly reports on the recent trends in the incidence of occupational heat disorders over the last couple of years in Japan and secondly provides an overview of the national administrative measures for occupational heat disorder prevention that have been taken so far by the Japanese Ministry of Health, Labour and Welfare (MHLW). On the basis of these findings, the author discusses how we should promote the preventive measures against occupational heat disorders, particularly focusing on how we should evaluate the effectiveness of products to protect against occupational heat disorders as preventive measures. It is concluded that a comprehensive and multiple assessment approach consisting of physical, physiological and field studies is required to address this challenging issue.

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Although occupational exposure to lead has declined dramatically since the establishment of better occupational hygiene and the improvement of standards, chronic exposure at a low level has remained a public health problem in many societies. Because many adverse pregnancy outcomes have been reported at ‘acceptable’ blood lead levels (≤5μg/dl), occupational health policymakers should improve the industrial standard of lead exposure for female workers of reproductive age. To achieve this goal, there is a need to carry out more studies on pregnant female workers in lead-related industries to find a safe level for them. In addition, blood lead screening programs for female workers should be considered on regular bases during reproductive age.

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To prevent poor mental health status in workers, it is necessary to minimize workplace stress and strengthen the stress resilience of individual workers. We focused on the sense of coherence (SOC) as an individual stress-coping ability and discussed SOC and occupational stress. Furthermore, we investigated previously published studies of resilience, which is a similar concept to SOC that has recently gained attention, and of occupational stress. The results indicated that specific support that was designed to increase SOC and resilience to prevent poor mental health status required the construction of a program including a cognitive-behavioral therapy approach, improvements to daily living habits, and acquisition of communication skills and that the effects of this program then need to be verified.

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The shrinkage of the Aral Sea has been called the biggest environmental disaster of the 20^th century. The Aral Sea came under the administration of Kazakhstan and Uzbekistan after the collapse of the Union of Soviet Socialist Republics in 1991. People living near the Aral Sea complained of health problems. The aims of this study were to evaluate the potential causes of these problems and how they may be remedied. We conducted a large-scale epidemiological study from the beginning of 1999 in Kazakhstan; the case region was near the Aral Sea and the control region was about 500km east of the case region. The subjects were 486 randomly selected schoolchildren in each region for a total of 815 children (383 cases and 432 controls were accepted into the study). The study parameters were anthropometric variables, hematological values, respiratory function, and renal function, in addition to a questionnaire on socioeconomic data and food intake. Body mass index was not significantly different between the two regions. The incidence of anemia was high: 62% in the case region and 39% in the control region. With regard to renal function, both urinary N-acetyl-β-D-glucosaminidase and β₂-microglobulin were significantly higher in the case region than in the control region. Evaluating respiratory function, we found that the prevalence rates of a restrictive pattern were 10.6% and 2.6% in the case and control regions, respectively. The obstructive pattern had a low incidence and did not differ significantly between the two regions. The subjects consumed minerals and vitamins in larger amounts in summer, except for vitamins A and D, which were taken more in winter. Sodium concentrations, determined in drinking water, blood, urine, and hair samples, in the case region were higher than in the control region. Two years after the initial assessment in the same children, anemia and renal function had improved. We considered that the health problems that directly correlated with the shrinkage of the Aral Sea might be respiratory dysfunction, caused by particulates, which was much increased after the shrinkage of the Aral Sea. We planted special local trees, saxaul, in one village in order to reduce particulates.

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Sleep disordered breathing (SDB) is a condition resulting in overall decreased sleep quality. Many people worldwide continue to be undiagnosed and untreated for SDB, a major public health issue that leaves them at increased risk for accidents and cardiovascular disease. Evaluation of the efficacy of various survey methods to identify those at increased risk for SDB highlights the benefits of screening. It is highly recommended that early identification and treatment be carried out. The beneficial effects of maintaining the overall health of the population by focusing on prevention and identification through screening in the present decrease the risk of life-threatening situations resulting from SDB in the future.

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Over the last decade, the agricultural work environment has undergone significant changes regarding types of employment contracts and working conditions. Since the revision of the Agricultural Land Act in 2009, it has become possible for inexperienced companies to enter the field of agriculture. As the structure of the agricultural industry in Japan changes, the issue of occupational health is receiving increasing attention among Japanese agricultural employees. Because almost all Japanese farmers have been self-employed for decades, the regulation of occupational safety and health for agricultural workers has not specialized in agricultural worker management. This paper discusses issues pertaining to agricultural workers’ occupational safety and health that are now arising along with such social changes.

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From 1978 to 2014, I was engaged in parasitology education and research at Juntendo University School of Medicine. During this period, I conducted research in the United States from 1985 to 1987. Furthermore, from October 1991 to March 1992, I was dispatched to the Federal University of Pernambuco in Brazil as a parasitology expert on an international project through the Japan International Cooperation Agency. I would now like to trace the research conducted by our research group, including that in the United States and Brazil.
The main topics of this paper are as follows:
1. Mitochondrial respiratory chains from the larval and adult stages of Ascaris suum, with special reference to electron transfer complex II and quinone components, both of which are key molecules in aerobic-anaerobic transition in nematode energy metabolism.
2. The respiratory chain in mammalian mitochondria and mitochondrial diseases caused by respiratory chain deficiencies, which I studied in the United States.
3. The mitochondrial respiratory chain of the free-living nematode Caenorhabditis elegans as a model of Ascaris larval-stage mitochondria.
4. Adult A. suum muscle-derived soluble cytochrome b₅: a key cytoplasmic molecule for adaptation to environmental hypoxia.
5. The functions and morphology of mitochondria in adult Paragonimus westermani, which make the host’s lung more habitable by forming cysts, the oxygen tensions of which are higher than those in the small intestine.

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Extramammary Paget’s disease (EMPD) is a cutaneous malignancy which is characterized by growth of Paget’s cells in anatomical sites other than breast skin. The areas of predilection for the disease are usually vulva, axilla, and the perianal region. Bladder metastasis is very rare, because metastasis most commonly occurs in lymph nodes. Here we show a rare case of bladder metastasis of EMPD of the vulva. A 77-year-old man was referred to our hospital with erosion of the penis. Surgical resection was performed as a treatment under the diagnosis of EMPD. One year later, an abdominal CT showed a left hydronephrosis and thickening of the bladder wall, where cystoscopy revealed irregular mucosa on the left side of the bladder wall. Pathologic examination with immunohistochemical stains of bladder mucosa showed bladder metastasis of Paget’s disease of the vulva. Occasionally, the Paget phenomenon is observed from the external urethral orifice to the vulva in transitional cell carcinoma of bladder. Paget phenomenon and EMPD are histochemically and symptomatically very similar, and differentiation between the two is essential. CK20 and GCDFP-15 staining are used for such differentiation, and pathologic examinations of immunohistochemical stains effectively diagnose EMPD.

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A 75-year-old woman presented with loss of consciousness to our hospital. Her electrocardiogram on admission showed negative T waves in III, aVF, and V_1～5 leads. Echocardiography indicated pulmonary hypertension with estimated right ventricular systolic pressure (RVSP) of 58 mmHg. Contrast-enhanced computed tomography showed the presence of a left pulmonary artery thrombus. Therefore intravenous anticoagulant therapy was started and the RVSP gradually reduced to 42 mmHg at 45 days after admission. With the reduction of RVSP, the negative T waves of the chest leads gradually disappeared from the left-sided leads to the right-sided ones on the horizontal plane of chest leads, whereas those of the limb leads gradually disappeared from the leftward axis of aVF (+90°) to the rightward ones of III (+120°). These findings suggest that the disappearances of negative T waves from left to right leads may result from the decreased right heart overload.

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Society’s industrialization and constant need for new products and components have increased the number and concentration of toxic substances that women are exposed to in their environment and workplaces. For decades, metal toxicity has remained a topic of concern for its effects on pregnant women. Although the level of exposure to many toxic metals has decreased sharply, research has revealed the impact of low-level metal exposure on different aspects of pregnancy. Lead is one of the toxic metals for which the effects on the human reproductive system have been intensively studied. The US Centers for Disease Control and Prevention have recommended a blood lead level of < 5.0 mg/dl as a screening action guideline in pregnant women. However, many studies have shown the adverse effects of lead on several human reproductive outcomes, such as low birth weight, preterm rupture of the membrane, and pregnancy hypertension, even at the ‘acceptable’ level of blood lead. This supports a reappraisal of the ‘safe’ or ‘acceptable’ level.
We aimed to conduct a review of our several-year-long longitudinal study on prenatal metal exposure and pregnancy outcomes.

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After the discovery of adult stem cells, these cells became the subject of intense experimental and clinical investigation for tissue regeneration. Bone marrow-derived adult stem cells consist of hematopoietic and mesenchymal stem cells. In 1997, Asahara’s group found vascular stem cells named endothelial progenitor cells (EPCs) within the hematopoietic stem cell population. After the identification of EPCs, investigators focused on their involvement in the treatment of ischemia and tissue regeneration. After injury or ulceration, bone marrow-derived EPCs are mobilized into peripheral blood and recruited to the foci of pathophysicological neovascularization and reendothelialization, thereby contributing to vascular regeneration and wound healing. Topical application of EPCs and their injection in tissue regeneration have shown success in preclinical studies and human clinical trials and are now under investigation by various facilities. However, in certain diseases, EPCs are reported to have impaired mobilization, proliferation, adhesion, differentiation and tubular formation. In this review, we focus on the biology of EPCs and the future possibilities of EPC therapy for therapeutic vasculogenesis.

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In the 1970-80s, Japan developed various vaccines ahead of the rest of the world. DPT vaccine (diphtheria, tetanus, and pertussis) and Japanese encephalitis vaccine were introduced abroad from Japan. In addition, the Japanese Oka strain used for varicella vaccine is the only strain recommended by the World Health Organization (WHO). However, problems related to vaccination such as aseptic meningitis with MMR (measles-mumps-rubella vaccine) subsequently occurred. As a result, in Japan in the 1990s, new vaccines were not developed and vaccination policy stagnated. On the other hand, many countries around the world promoted vaccination policies from the viewpoint of preventive medicine and developed various vaccines that were incorporated into routine immunization. However, the vaccine gap in Japan has begun to improve recently. Specifically, vaccines that are recommended increased in number and the immunization schedule became complicated. In terms of the past and present vaccination policies in Japan, this session gives an outline of the effects of vaccines and issues regarding vaccines and immunization schedules. Unfortunately, rubella was prevalent in Japan last year, and cases of congenital rubella syndrome have increased. Therefore, we must provide education on the importance of vaccination and herd immunity in Japanese vaccination policy.

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Infectious diseases related to vaccines are defined as ‘preventable diseases’ by the WHO. Although rubella is a preventable disease, an outbreak of it occurred in 2012 in Japan. The number of reported patients was as high as 14,357 and subsequently 32 babies with congenital rubella syndrome (CRS) were born. There is a notable background to this outbreak of rubella, including the history of rubella vaccination, which needs to be understood.
In Japan, rubella vaccine was first administered in 1976 for only girls in junior high schools. Although MMR vaccine was started for both boys and girls in 1989, it was canceled in 1993 due to anxiety about its side effects, such as aseptic meningitis. Although it was started again in 1995, there were gaps in some adults between 20-40 years old who could not receive a vaccine and who have an elevated risk of rubella infection. At the time of the above-mentioned outbreak, this population led to an increase in the number of patients. The importance of rubella vaccine was thus confirmed.
Hepatitis B is one of the major vertically transmitted infections because we reduced the number of HB patients by using better transfusion systems. In 2013, the government changed the protocol to prevent vertically transmitted infection of HBV, which will be more effective for prevention.
Influenza vaccine is the most commonly administered vaccine during pregnancy due to its immunotolerance. It is known that influenza vaccine can be given safely throughout pregnancy, and there are some additional effects.
Finally, a recently investigated vaccine is one for cytomegalovirus (CMV). CMV infection during pregnancy induces congenital CMV infection with neurodevelopmental insufficiency and deafness. Although the rate of positivity for CMV antibodies in adults was previously as high as 90%, it decreased to around 65% for environmental reasons. Manufactured CMV vaccine is in a phase II clinical trial. There will thus be some delay before its potential use in clinical practice. This paper is intended as a review of the history of vaccination and confirmation of the efficacy of vaccines in clinical practice.

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Cancer immunotherapy is currently recognized as the fourth most common therapy for cancer, after surgery, radiotherapy, and chemotherapy. Cancer vaccination is a therapeutic approach that involves attacking cancer cells by enhancing the immunity of cancer patients. The use of cancer immunotherapy to induce a therapeutic antitumor immune response in the patient has huge potential for complementing traditional cancer therapies.
Tumor antigens have been identified in a variety of carcinomas. Since the recognition of cancer-associated antigens by cytotoxic T cells (CTL) was first reported by Van der Brugeen et al. in 1991, numerous clinical trials have been conducted to demonstrate the efficacy of cancer vaccination. In 2010, the US Food and Drug Administration (FDA) approved the vaccine Sipuleucel-T (Provenge^®) for the treatment of prostate cancer. Ipilimumab (Yervoy^®) is an anti-CTLA-4 antibody preparation that targets cytotoxic T-lymphocyte antigen 4. In 2011, Ipilimumab was approved in both Europe and the USA for the treatment of malignant melanoma. As a result, cancer immunotherapy has attracted attention worldwide, including in Japan.
Peptide vaccination, which is one form of cancer immunotherapy, is a promising approach in which a clinical response is expected. Activated CTLs, which are antigen-specific, are generated using the human leukocyte antigen (HLA) -restrictive epitope peptide derived from a tumor antigen identified by exhaustive gene analysis. In Japan, peptide vaccination is a form of therapy that is currently the focus of intense research.
Cancer vaccination is a therapy that can offer prolonged overall survival whilst maintaining quality of life. However, the efficacy of cancer vaccination has not yet been proved, with the exception of for particular malignant tumors. If a biomarker for responders of cancer vaccination can be discovered, the efficacy of cancer vaccination should be established. We anticipate the results of an investigation by clinical trials using cancer vaccination.

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When it comes to vaccination, you might have heard about Edward Jenner when you were students. Based on experimental findings revealing that individuals with a history of cowpox virus infection were less likely to be infected with smallpox, and smallpox infection only led to mild infectious symptoms without resulting in death, researchers investigated the application of vaccines to treatment. It appears that experiments performed by other physicians caused numerous deaths. Jenner vaccinated humans against smallpox using cowpox virus. This attempt, currently referred to as vaccination, has proved to be successful and saved many people’s lives. Consequently, in May 1980, the WHO declared that smallpox had been eliminated.
Thus, appropriately used vaccination is highly effective and markedly benefits society. However, I think that we need to obtain accurate information on vaccination, such as the individuals for whom each type of vaccination should be indicated, the timing of its use, its limitations, and side effects. As is the case with any drug, no vaccine achieves the same effects in every person, and the beneficial and side effects of vaccines may differ according to each individual’s immune state. The purposes of vaccine use also differ according to the target person and area.
In vaccination, foreign substances (nonself antigens) that do not exist in the human body are administered through the skin, nose, or mouth, or using intramuscular or intravenous injections, in order to induce the involuntary activation of an individual’s immune function. In other words, vaccine is the key player to perturb the immunological milieu and therefore initiates break tolerance.
Therefore, vaccination may cause severe side effects, which are sometimes fatal.
In this public lecture on vaccination, other speakers have reported the latest relevant information, but I will describe the neurological side effects of influenza vaccine. I am also going to talk about the neurological side effects of cervical cancer vaccine, which has been a hot topic in Japan recently, the new reporting system in post-vaccination inflammatory CNS demyelinating event such as ADEM, and the history of therapeutic vaccination against multiple sclerosis, which is my main research theme. Also I discuss the failed vaccination trial against Alzheimer’s disease, which is becoming increasingly prevalent worldwide, including Japan. I enclosed lead out in these studies, and how to tackle issues associated with vaccination, whose frequency is expected to increase globally. We have learned that a risk (疫eki; plague ) and a benefit (益eki; value) are two sides of the same coin. To protect ourselves from disease, we need to properly understand immunity and excessive immunological responses.

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