On 9th March 2015, Dr. KALES Stefanos, Associate Professor of Harvard Medical School and Harvard School of Public Health, visited the Juntendo University and gave a talk, entitled “Screening for sleep disordered breathing (SDB) in truck drivers in the US” (Figure-1). After Professor DAIDA Hiroyuki, Director of Juntendo University Hospital & Professor of Department of Cardiovascular Medicine, kindly introduced him with a warm-hearted welcoming speech, Dr. Kales started his talk by referring to the current situation in the US; obstructive sleep apnea (OSA), one of major diseases that cause SDB in the adult population, is characterized by excessive daytime sleepiness, psychomotor deficits, impaired vigilance, and sleep which is frequently disrupted by SDB. This constellation of symptoms increases the risk of traffic accidents. It was estimated that 10-30% of truck crashes are associated with driver fatigue/sleepiness. Similar issues are also shared by Japanese truck drivers, as the prevalence of SDB in truck drivers is estimated to be as high as 25% in both countries. Obesity is also a common risk for SDB, and furthermore, OSA is “under-recognized” in both countries. On the other hand, many Japanese truck drivers with SDB are not obese. Dr. Kales emphasized that screening for SDB in truck drivers is an urgent issue in the US, as well as in Japan, and he also described some potential future approaches to screening for SDB, using psychomotor vigilance test and driving simulator. In addition, he described standard occupational health and safety tools, including education, administrative controls, OSA screening, drug tests, driver monitors, and vehicle controls. By summarizing these various approaches, Dr. Kales proposed an overall approach, based on the “Swiss cheese model”: you may be able to look through one of many holes on a single slice of Swiss cheese, but you cannot do so through several layers of Swiss cheese slices in series (Swiss cheese model theory, Figure-2). Likewise, any one of the individual approaches to screening SDB cannot completely identify all individuals who are at high risk for traffic accidents. However, a combination of those tools could considerably decrease the risk of traffic accidents. Dr. Kales’s talk clearly depicted that SDB is socially under-recognized although it is one of the socially un-ignorable causes of traffic accidents, and effective diagnostic and therapeutic strategies are already established, suggesting that we can reduce traffic accidents now. Because the US and Japan share many common issues, Dr. Kales and Professor Tanigawa launched a global project to tackle SDB, attempting to reduce traffic accidents. We held a symposium last October at the Harvard School of Public Health in Boston and had a discussion of issues regarding why companies, governments and/or societies in both countries were reluctant to introduce more aggressive SDB screening programs. We are not describing it in detail here, but we, faculty members at both Juntendo and Harvard, will continue to work hand in hand to establish the evidence, showing that SDB screening is effective and can decrease accidents among truck drivers in both countries. Herein, it should be noted that International Association for Traffic and Safety Sciences (IATSS) supported not only the two meetings, one in Harvard School of Public Health and another in Juntendo University, but also the associated research project organized by Professor Tanigawa. The talk given by Dr. Kales attracted as much as 48 participants, even including two officers of the Traffic Bureau of the National Police Agency, which encouraged us greatly. Several medical students of Juntendo also joined the talk and enjoyed the discussion. We believe that this surely provided them with a unique opportunity to consider global issues and enlarge their horizons for their own (View PDF for the rest of the abstract.)
“The awardee of Santosh Nigam Memorial Outstanding Young Scientist Award is Dr. Min Liu from Juntendo University, Tokyo!” This announcement reached our ears at the party on the Danube River, Hungary. Min Liu, who was sitting next to me, was almost crying upon hearing this announcement. Probably she was remembering the long tough days we spent preparing to publish our exciting data in a Journal1). This international conference on lipid mediators is held every two years at various locations in the world, and this year we had the 14th conference with more than 300 researchers at Budapest, Hungary. Professor Shuh Narumiya of Kyoto University received a Lifetime Achievement Award and Professor Timothy Hla of Weill Cornell Medical College received an Outstanding Achievement Award, both of which had been announced earlier on the web page. The Santosh Nigam Memorial “Outstanding Young Scientist” Award is to recognize the great contribution of the Late Professor Santosh Nigam from Berlin to this series of conferences, and awarded only to one presentation of a total 220 presentations. Dr. Min Liu, a former research associate of the Department of Molecular and Cellular Biochemistry, Juntendo University Graduate School of Medicine, successfully received this award on her excellent presentation entitled “Crucial role of the 12-HHT receptor BLT2 in epidermal wound healing”. At the party on the ferry boat on the Danube River, Mrs. Nigam honored Min Liu for her finding on the roles of lipid mediators in skin wound healing processes. We are now working to generate a new drug for skin ulcers based on Min Liu’s findings2).
We applied for funding in the form of Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, to support our project regarding intractable itch, and were awarded funds in 2013. This project will be financially supported for 5 years. To progress in this project, we held the 1st and 2nd Workshops and the 1st Symposium from 2013 to 2014 in fine meeting places of Juntendo University. In this “What’s New from Juntendo University, Tokyo”, we report selected aspects of the 1st Symposium and the 2nd Workshop and advances in the field of itch research.
An effective blood-stage vaccine remains elusive but necessary if we are to reduce malaria morbidity and mortality. The SE36 antigen derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum remains a promising blood-stage malaria vaccine candidate. The protective efficacy of BK-SE36, SE36 recombinant protein and aluminum hydroxide gel, is continuously being studied in clinical trials. However, the efficacy of BK-SE36 may still be improved with the use of DNA sequences containing CpG motifs that can selectively promote cellular and/or humoral immune responses. Preclinical studies in non-human primates show promising results. A clinical trial of the vaccine candidate BK-SE36/CpG in a malaria-exposed population is awaited as this can give valuable clues on the immune responses towards K3 CpG formulation in malaria-endemic populations.
Malaria is caused by the Plasmodium genus in the phylum Apicomplexa, and P. falciparum is the most malignant parasite species. Because the malaria parasite possesses antigenic variation through a variety of gene families, it can evade human immune surveillance, which makes vaccine development difficult. In addition, the parasite quickly acquires drug resistance/tolerance to existing antimalarial drugs by mutating its genome and changing its gene expression levels. In this context, there is no effective vaccine or drug available for malaria control. In 2002, sequencing of P. falciparum genome was completed and it appears that approximately 5,300 genes are coded in its genome, of which 60% have unknown function. Because genetic manipulations such as knock-in, knockout and the transient expression of foreign genes are applicable to the Plasmodium species, we anticipate that understanding of the parasite biology will be accelerated and that the accumulated knowledge will soon lead to identification of new vaccine targets or drugs. However, the malaria burden still threatens human life because the current genetic tools are not sufficient to unravel Plasmodium biology; thus, novel genetic tools are necessary. Recently, we have succeeded in the creation of “malaria mutator”. Malaria mutator showed a mutation rate that was 80 times higher than that of the wild-type parasite. We readily isolated drug-resistant parasites from the malaria mutator library in a few rounds of screening. Whole-genome sequencing and subsequent single nucleotide polymorphism (SNP) analysis identified candidate causative gene mutations for drug resistance. In this review, we introduce our malaria mutator and discuss its usefulness for Plasmodium biology research compared with conventional tools. We describe our recent attempt to deepen our understanding of Plasmodium biology, including drug resistance and immune evasion by using malaria mutator.
The Global Programme to Eliminate Lymphatic Filariasis (GPELF) inaugurated in 2000 is a unique ‘adventure’ in a sense that it targets one of the most neglected diseases at a global scale. To accomplish this ambitious program, not only health professionals but community people have been playing an essential role in distributing a huge number of antifilarial drugs. Approximately 500 million people are treated annually worldwide, including numberless ‘neglected’ people in remote rural areas. GPELF is said to be one of the most rapidly expanding global health programs in the history of public health. With its cost-effective, systematic mechanism, 60 of 73 endemic countries are conducting national ‘mass drug administration’ campaign, and 15 of them are now close to the elimination of filariasis. How can this kind of program be implemented and maintained for more than a decade? What are the achievements and their public health and scientific implications? This review summarizes these topics with emphasis on key researches and field operations which have facilitated this unprecedented program.
Chagas disease, or American trypanosomiasis, is caused by the parasitic protist Trypanosoma cruzi. 10 million people are estimated to live with this disease. Chagas disease is endemic to the Americas, which corresponds to the distribution of the insect vectors, blood-sucking triatomine bugs. The presence of many mammalian species as reservoir hosts and the occurrence of a long asymptomatic phase of infection that may last more than 10 years make control difficult. In the United States, domestic transmissions from triatomines to humans are rarely reported, but it is estimated that there are 300,000 people living with Chagas disease among Latin American immigrants. Patients with Chagas disease are also found outside the Americas, as well as in Japan, via international migration. Thus, there is a growing need to understand the current situation in non-endemic countries in terms of establishing better preparedness against the incursion of Chagas disease.
Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, is a severe disease in humans and other primates caused by viruses in the genus Ebolavirus; the most pathogenic variants of the virus are the members of the species Zaire ebolavirus, with fatality rates as high as 40-90%. The 2014-15 Ebola outbreak is the largest in history, and there is an urgent need to develop effective countermeasures against EVD. Viral proteins such as VP35 block some of the interferon pathways in the host, and these mechanisms contribute to efficient viral replication in dendritic cells, monocytes, and macrophages. EVD is associated with rapid viral dissemination and marked dysregulation of the immune and vascular systems, which leads to hemorrhage and multiple organ failure. ChAd3-EBOV and VSV-EBOV have shown the most promise as vaccine candidates for EVD. Favipiravir, ZMapp, and TKM-Ebola-Guinea are emerging as promising drug candidates. Increasing data on the virus and EVD pathogenesis will accelerate the establishment of vaccines, antiviral drugs, and other novel strategies to counter EVD. This review provides an outline of the history, pathogenesis, and treatment of EVD and summarizes current efforts to develop vaccines against EVD.
Dengue is a mosquito-borne disease that is caused by the dengue virus (DENV) and that represents an important public health problem in tropical and subtropical countries. Because it is carried by mosquitos, there were no cases of domestic infection in Japan for the last 70 years. However, 162 persons were infected with DENV in Japan last year, possibly due to the changes in climate or human migration. Research on dengue has a long history, but many important questions have not yet been answered. For instance, it is still unknown why severe dengue occurs when a patient is secondarily infected with a different serotype of DENV. It is believed that severe dengue is the result of vascular leakage induced by an excessive host defense reaction, but it remains unknown what triggers the change in vascular permeability. DENV-infected patients often show thrombocytopenia, a typical symptom of dengue, but it is not known what causes the thrombocytopenia and if there is a correlation between thrombocytopenia and vascular leakage. This review describes the features of DENV infection and the current state of developing dengue vaccines and treatments.
Objective: Juntendo Tokyo Koto Geriatric Medical Center (KGMC) has been operated for more than ten years from June 1st, 2002. We analyzed and reviewed dialysis patients admitted to our hospital for ten years, and compared the results with a nationwide statistical survey performed at the end of 2012 in Japan. Patients and Methods: The subjects were 2,011 patients (1,281 men and 730 women) undergoing maintenance dialysis from June 2002 to December 2012. There were 4 patients who underwent peritoneal dialysis (PD). We evaluated the each patient statistically every year, and analyzed the underlying disease and cause of death during hospitalization. Results: The number of all and new dialysis patients over the ten-year period increased. The total number of new patients each year was 337 (226 men and 111 women) with the mean age of new patients at 70.8±11.4 years (69.0±11.3 for men vs. 74.4±10.5 for women) and that of all patients at 71.9±10.8 years (70.4±10.6 for men vs. 74.9±10.8 for women). The percentage distribution of all patients over the ten-year period who underwent dialysis according to the underlying disease showed that 58.3% had diabetic nephropathy (DN), 19.5% had nephrosclerosis (NS) and 10.5% had chronic glomerulonephritis (GN). The most frequent cause of death during hospitalization in all years was infection (22.6%), followed by malignancy (17.6%), and cardiac failure (16.0%). Conclusions: The mean age of patients entering maintenance dialysis treatment decreased to 68.8±11.7 years in 2012 at KGMC, which was nearly in accordance with the mean age of dialysis patients in Japan. The recent increase in aged patients undergoing hemodialysis was attributed to the high incidence of DN. It has been the most common cause of end stage kidney disease (ESKD) in patients receiving chronic dialysis treatment, and this accounts for up to 50% of ESRD patients over the period.
Objective: Authorized pathological classification schemes pay much attention to glomerular changes but little to renal interstitial injuries in patients with lupus nephritis (LN). Since the degree of interstitial injury may be a better renal predictor than glomerular damage in some chronic glomerular diseases, we explored the clinical significance of interstitial fibrosis in the prognosis of LN. Materials: Forty-three patients of systemic lupus erythematosus (SLE) who had undergone renal biopsy were enrolled in the present study. Methods: All patients were categorized using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and their interstitial fibrosis severity was semi-quantitatively graded. Clinical data was evaluated at the time of renal biopsy and at the last follow-up period. Results: In each group classified by the ISN/RPS classification, renal function had no statistical difference at both times. When all patients were divided into interstitial fibrosis grades, there was no significant difference in renal function at the time of renal biopsy. However, renal function in patients with severe fibrosis at the last follow-up period was significantly worse than those in other fibrosis grades. On the other hand, the serological activity of SLE had significantly ameliorated after treatments in both categorizations. Conclusion: It is concluded that severe interstitial fibrosis may be a renal predictor apart from glomerular lesions and the serological activity of SLE.
Objective: We started a skeletal related events (SRE) management team to conduct rehabilitation interventions safely in cancer patients with metastatic bone lesions. SRE conferences were held 24 times from April 2011 to April 2012. Based on this experience, we investigated how the conferences benefited these patients. Participants: 78 individual patients (36 males and 42 females; aged 12-84 years, mean 63.6 years) were discussed in SRE conferences. Some became the subject of discussion repeatedly, and a total of 120 patients were discussed. Methods: This report analyzed retrospectively the effects of SRE conferences on the patients. Results: Primary cancers included breast cancer in 21 patients, lung cancer in 19, renal cancer in 7, liver cancer in 7, prostatic cancer in 6, esophageal cancer in 3, and gastric cancer in 3, and others in 12. No patients sustained pathological bone fracture during rehabilitation interventions. Rehabilitation achieved the goal of mobility in 75% of patients. Through substantial discussions within the interdisciplinary team, 16 patients with critical bone lesions assumed anti-gravity posture on average 4.4 days after (minimum 6 days before, maximum 23 days after) completion of radiotherapy. This was clearly earlier than the empirical schedule of around 2 weeks. The proportion of patients who were discharged to their own home increased significantly since SRE conference was started, compared to the pre-SRE conference period between 2006 and 2007. Conclusion: The present study suggests that implementation of SRE conference for cancer patients with bone metastases is effective to improve activity level with low risk of inducing pathological fracture, and is useful to achieve patients’ goals including mobility improvement and independent ADL.