Alfred G Knudson (1922-2016) was a man of great insight into the cancer genetics and a personal mentor of the author. Knudson developed the two-hit hypothesis (1971). From this hypothesis, the concept of tumor suppressor gene was led. In 1954 (my birth year), a Norwegian pathologist, R. Eker found an animal model of inherited tumor. The Eker rat developed bilateral, multiple and dominantly inheritable renal tumors. Utilizing syntenic homology between human and rat, a germline insertion was identified in the homologue of tuberous sclerosis complex (TSC) 2 gene (Tsc2) as the tumor predisposing mutation of the Eker rat. We, in researching hereditary kidney cancer in Eker rats, found that the product of the gene Erc, which appears with high frequency in simultaneous progressive process cancer, is secreted in the bloodstream, thereby providing a possible method for blood diagnosis. We reported that N-ERC/mesothelin could be a useful serum tumor marker for mesothelioma and have developed an ELISA kit (IBL. Co., Ltd. Gunma, Japan). ʻEnvironmental carcinogensʼ came to light in 1775 when the British surgeon Percival Pott reported scrotal cancer associated with chimney sweeps in ʻcancer stimulated by chimney soot.ʼ In 2003, I was immersed in the 100^th anniversary event of the worldly renowned cancer pathologist Tomizo Yoshida (1903-1973), who paved the way in unveiling the mechanism of cancer. Apart from being a cancer pathologist, Tomizo Yoshida was also a thinker who eloquently used analogies of cancer to explain his outlook on life. Cancer Philosophy (2004), considers cancer as a science along with the political philosophy which was suggested by Shigeru Nambara (1889-1974; the first president of the University of Tokyo after World War II) at the start of my adolescence. Cancer Philosophy Clinc was started at Juntendo University at 2008. I did compulsory retirement this March and gave a speech. I will review on “Hereditary cancer → Environmental carcinogenesis → Cancer Philosophy Clinic”.

At the retirement from the Juntendo Graduate School of Medicine, I here review my 40-years currier as a psychiatrist and realize that working in this field is very worthwhile and attractive not only for contribution to improving quality of patients’ life by treating mental illness but also for making me grow to have a wider view as a human. Accordingly, the patients and their family are my teacher in real-world. Also, I am not sure whether I could complete my term until retirement, if my colleagues were not passionate and supportive as they were. In this sense, my colleagues were my precious treasure in life.

Forty-one years have passed, since I began my career as anatomist at the Department of Anatomy in alma mater after graduation from the Faculty of Medicine, University of Tokyo in 1978. Twenty-nine years have passed, since I became the Professor of Anatomy at the Juntendo University. I conducted academic activities in four fields. 1) In the microscopic research on the kidney, I discovered the mechanical function of mesangial cells to counterbalance the expanding force of blood pressure in 1987. Since then I studied the microscopic morphology of renal glomerulus, and of the interstitium and blood vessels in various tissues, 2) In the macroscopic research with my colleagues, I studied the morphology of the peripheral nerves and arteries. In recent years, the isolated muscle specimens became an excellent tool to analyze the functional architecture of skeletal muscles. 3) In the history of medicine, I studied especially the history of anatomy, of medical education and of Western medicine in general. 4) In the academic and social education of the anatomy and body donation, I have published many academic textbooks, including 17 titles and 35 editions of the translated and/or supervised textbooks of anatomy, 17 titles and 26 editions authored and/or edited textbooks of anatomy and biology. I have long been engaged in the activities of Tokushi Kaibo Zenkoku Rengokai [National Confederation of Anatomy Body Donation], and served the executive director from 2002 to 2006 and the chairman from 2006 to 2010. I experienced that the body donation became increasingly popular so that the proportion of donated cadavers to the total dissected ones increased from 42% in the 1983 to more than 99% in the 2018.

Although the current risks of viral transmission through blood components are very small, mistransfusion, in which the wrong blood is transfused to the wrong patient, remains the most common type of error in transfusion practice. Many studies have revealed that mistransfusion occurs resulting from failure to perform the final patient identification check at the bedside. Thus, pre-transfusion check at the bedside is the most critical step for the prevention of mistransfusion. An electronic identification system (EIS) is ideally suited to pre-transfusion check requirements. An experience at the Juntendo University Hospital showed that the bar code-based EIS works well on a hospital-wide basis in the setting of regular allogeneic blood transfusion, preoperative autologous blood donation and transfusion, pediatric transfusion, and hematopoietic progenitor cell infusion at the bedside. Approximately 110,000 blood components have been transfused over a 10.5-year period without a single mistransfusion. The overall compliance rate with electronic pre-transfusion check at the bedside was 98.2%. Human error was the most frequent cause of errors leading to failure of the ‘second’ electronic pre-transfusion check. If we want to reduce the risk of mistransfusion to improve transfusion safety, we have to address the issue at the hospital level, with a system-based approach.

Here, I describe and summarize the author’s research in Juntendo during the past 38 years. The author joined the Department of Internal Medicine and Rheumatology of Professor Yuichi Shiokawa in 1981. Prof. David TY Yu taught me basic research on spondyloarthritis (SpA), in particular Reiter’s Syndrome, at the University of California Los Angeles (UCLA) from 1981 to 1984. After the author’s return, various milestones and clinical researches in rheumatic diseases have been accomplished and published, respectively. Such results and achievements, including new findings, have significantly influenced domestic as well as foreign investigations. Currently, the author acts as chairman of the Japan Society of Spondyloarthritis and aims to improve the understanding and appropriate treatment of SpA.

Objective: This study aimed to evaluate runners in a mountain ultra-marathon in terms of changes in their urine components and characteristics, in order to facilitate the creation of guidelines for running such races safely.

Design: This was a prospective observational study of 24 participants in the Trans Japan Alps Race 2014, a 415-km mountain ultra-marathon.

Methods: Urine samples were collected from participants 5 times: before the race, at 3 checkpoints (CP) mid-race (CP1: elevation of 2,870 m, 192.8 km from the start; CP2: 1,424 m, 236.8 km; CP3: 2,610 m, 290.7 km), and at the finish line. Urinalysis was performed immediately after collection to qualitatively measure 10 urine components.

Results: Urine samples of participants who completed the race tested positive for urobilinogen at a higher rate than before the race (0%), at CP2 (66.7%; p=0.008), CP3 (42.9%; p=0.031), and at the finish line (61.5%; p=0.008). Samples collected at CP3 tested positive for ketone bodies at a higher rate than before the race (50% vs. 0%, p=0.016). Significant correlations between protein and specific gravity were observed at each measurement point (before the start, r_s=0.733, n=14, p=0.003; CP2, r_s=0.627, n=12, p=0.029, CP3, r_s=0.778, n=14, p=0.001, finish, r_s=0.754, n=13, p=0.046).

Conclusions: Our findings suggest that runners in ultra-marathons experience hemolysis as a result of mechanical and physical stress, and have increased fatty acid metabolism. Impaired renal function may be detected by screening for urinary protein and specific gravity.

Objective: During colonoscopies, clinicians often find feces accumulated in the colonic diverticula. We hypothesized that these feces and potential changes in fecal microbial communities contribute to colon diverticulitis. The aim of this study was to investigate potential changes in the fecal microbiota in symptomatic uncomplicated diverticular disease by terminal restriction fragment length polymorphism (T-RFLP) analyses of fecal microbiota from patients with colonic diverticula, and stool samples.

Materials: Fifteen patients with colon diverticulum and 28 healthy volunteers were enrolled. The fecal samples were classified as follows: Group I, feces from a healthy individual; Group II, feces in colonic diverticula obtained during colonoscopy; Group III, feces from the natural defecation of Group II patients.

Methods: Fecal microbiota profiles were evaluated by T-RFLP analysis.

Results: T-RF patterns of fecal microbiota were divided into three clusters. Most Group I samples were included in clusters A and B, whereas most Group II samples were included in cluster C. Operational taxonomic units of 657 bp (p<0.05) and 955 bp (p<0.01) differed in abundance between patients with colon diverticulum and healthy individuals.

Conclusions: T-RFLP analyses revealed that the fecal microbial communities in patients with diverticular disease differed from those of healthy individuals, particularly for the operational taxonomic units of 657 and 955 bp. Changes in the fecal microbiota, including Lactobacillales and Clostridium subcluster XIVa, may play a role in diverticular disease.

Objective: Alpha-actinin (ACTN) 3 R577X polymorphisms have three genotypes: RR, RX and XX. Only RR and RX genotypes express ACTN3 protein in type II fibers. The purpose of this study was to clarify whether there are differences in ACTN3 protein expression levels and myosin heavy chain (MyHC) composition between RR and RX genotypes in Japanese college-level male sprinters.

Materials and Methods: Forty-three Japanese college-level male sprinters participated in this study. Subjects were genotyped for ACTN3 R577X using a real-time polymerase chain reaction assay. Furthermore, muscle biopsies from the vastus lateralis muscle were obtained from a subset of subjects who had R allele and gave their consent (4 RR and 9 RX). ACTN3 protein expression levels were assessed by western blotting. MyHC composition was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Results: There was no difference in 100-m sprint performance among RR, RX and XX genotypes in all 43 subjects. In 13 biopsy-sampled subjects, there was also no difference in 100-m sprint performance between RR and RX and ACTN3 protein expression levels tended to be higher in RR genotype than in RX genotype. Although there were no differences in the proportion of type I and II MyHC isoforms between both genotypes, RR genotype had a significantly higher proportion of type IIx MyHC isoform and a significantly lower proportion of type IIa MyHC isoform than RX genotype.

Conclusions: ACTN3 protein expression levels and the proportion of type IIx MyHC isoform are higher in RR genotype compared with RX genotype in Japanese college-level male sprinters.