A link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been suggested; however, the mechanisms are poorly defined because of the lack of an appropriate model. Previously, we reported a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4co/co; Lck-cre) and found that Smad4co/co; Lck-cre mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. These findings indicate that Smad4co/co; Lck-cre mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and furthermore, the disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contribute to a Th2 T-cell phenotype.
Diabetic nephropathy (DN) is increasing rapidly worldwide. In Japan, over the past two decades, the proportion of DN in patients with new-onset hemodialysis induction dramatically increased along with an exponential increase in the number of diabetic patients. Regarding the pathophysiology of DN, it was previously thought to be very simple, i.e. the development/progression of DN was able to be explained only in terms of hyperglycemia, genetic factors, and so on. However, it has become evident that many factors, such as advanced glycation end-products (AGEs), oxidative stress, and chronic inflammation, are involved in the pathogenesis of DN. With respect to progression process of DN, we thought it to be very difficult to halt the progression of this disease if the urinary excretion of albumin increased up to the level of macroalbuminuria (an albuminuria of more than 300 mg/g·Cr), a stage which has been called “the point of no return”. Now even diabetic patients with a nephrotic range of proteinuria sometimes regress to levels of normo- or microalbuminuria with the benefit of advances in diabetic treatment. This review article describes some of the knowledge that has been gained from our previous studies and also reviews advances in clinical and basic research in DN based on published literature over the past decades.
Osteoarthritis of the knee (knee OA) is an increasingly important public health concern, as the prevalence of the disease is increasing with the aging of society. It is considered to be one of the major diseases responsible for locomotive syndrome, defined as being restricted in one’s ability to walk owing to a dysfunction in one or more parts of the locomotion system. However, as no disease-modifying treatments for knee OA exist, all of the currently available treatments are symptom-modifying. Pain is the most prominent and disabling symptom of OA, and is also one of the factors predicting the progression of OA. There is an urgent need to improve our understanding of both the pathophysiology and the symptoms of the disease. Recently, the role of synovitis in OA has attracted particular attention, as synovitis has been revealed to be one of the potential indicators of knee pain and a predictive factor for both structural and symptomatic progression of the disease. In this review, we introduce the associations among pain, symptoms, and synovitis in patients from early- to end-stage knee OA, and also address future perspectives regarding the involvement of synovitis in the management of knee OA.
Twenty-five years have passed since I entered the teaching profession in Juntendo, and 40 or more years since I began to engage in research in graduate school. My major is psychology and my themes of research were classified into two topics. The first topic is moral development. I had been working on this topic since my thesis for my Master’s degree, which was based on Kohlberg’s theory, and the first research in Japan. I introduced his theory and carried out a number of studies related to moral development. I review the trends of psychological research on moral development as follows: 1. before Kohlberg, 2. Kohlberg’s theory, and 3. current trends - after Kohlberg. The second topic is interpersonal framework, which is based mainly on Bowlby’s attachment theory (internal working models (IWM), which is a mental representation and operates as a framework). I have carried out my research on nursing students in Juntendo as participants, and have been continuing these studies longitudinally after they graduated from university. I review adult attachment as follows: 1. Bowlby’s adult attachment theory and related research, 2. the stability and changeability of IWM over the lifespan, and 3. factors contributing to IWM or adaptation in adulthood.
In this review, I focus on three major subjects of my research life in Juntendo. The first subject, the work on which was carried out at Narashino campus, was purification and crystallization of iron-containing superoxide dismutase (Fe-SOD). Since we succeeded in the crystallization of Fe-SOD, we determined the three-dimensional structure of the enzyme by X-ray crystallographic analysis in collaboration with Dr. Mitsui (University of Tokyo), and then Prof. Gregory A. Petsko (MIT, USA). Finally, we succeeded in determining the three-dimensional structure of Fe-SOD for the first time. The second subject was determination of nitrated amino acids (Tyr34) in human recombinant manganese-containing superoxide dismutase (Mn-SOD). This modification caused inactivation of Mn-SOD and has been found in many disease states. Therefore, this modification has an important role for the process of oxidative injury in these diseases. The last subject was the establishment of a new oxidative stress marker, which was caused by reactive nitrogen species (RNS). We identified a major nitrated product of tryptophan residues in proteins reacted with RNS, 6-nitrotryptophan, and developed its specific monoclonal antibody. We successfully identified 6-nitrotryptophan-containing proteins in pathophysiological and physiological states of animals and also humans by the combination of the specific antibody and LC-MS/MS analysis. We believe that this technique could be a useful tool as a new oxidative stress marker and also a new tool to clarify new mechanisms of nitrative stress in vivo.
Just turn of the 21st century, Japanese government established the Basic Plan for the Promotion of Sports. This basic plan aimed to accelerate the realization of the Sport for All society in Japan. The Sport for All society means to prevail the enhancement of wellness and social welfare to all citizens through sport participation. In order to realize the Sport for All society, the sporting Utopia, the Sport Basic Act and Sport Basic Plan have been enacted after 2011 in Japan. This movement to realize the sporting utopia has become one of the main and serious political issues in industrial and post-industrial societies for the last two decades. This article is comprised of three phases such as sport policy, community sport clubs, and sport promotion. The author paid special attentions to comprehensive community sport clubs, so-called comprehensive clubs, which have been expected to accommodate local residents to develop sporting lifestyle. However, the recent global athletic medal races have become too excessive to keep most countries from reaching a sporting Utopia. Japan has been no exception. In this sense, 2020 Tokyo Olympic and Paralympic Games will be expected to create the legacies and become the catalyst for realization of the Sport for All society.
Objective: The aim of the present study was to investigate hidden distress originating from the expected pharmacological features in clinical practice using questionnaires, one of the best methods to communicate distress without the difficulties of verbal communication. Patients: We studied 57 Japanese outpatients with schizophrenia, including 21 taking only first-generation antipsychotics, 20 taking only sedative second-generation antipsychotics, 5 taking only non-sedative second-generation antipsychotics and 11 taking both types of antipsychotics. Methods: The questionnaire comprised from the Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM). The side effects scale from TSQM was further investigated with the Side Effect Questionnaire. Results: Regarding satisfaction, effectiveness were significantly higher in patients medicated with first-generation antipsychotics than in those medicated with both generations of antipsychotics. Convenience were significantly lower in patients medicated with both generations of antipsychotics than in those medicated with first-generation or sedative second-generation antipsychotics. No significant difference among the groups was found regarding side effects. Conclusions: For outpatients voluntarily receiving pharmacotherapy, side effects were not the main dissatisfaction factor because these were controlled to a certain extent in practical treatment. For these patients, convenience and effectiveness were the most important factors for their satisfaction.
Laparoscopic surgery has been widely applied to various surgical procedure, becoming standard procedure for colorectal and kidney cancer. Here, we describe a case of simultaneous laparoscopic surgery for synchronous colorectal and kidney cancer. A 70-year-old female was diagnosed with a tumor in the right lower abdomen. An abdominal CT showed tumors in the ascending colon and the right kidney. A colonoscopy demonstrated ascending colon cancer, and the patient was diagnosed synchronous ascending colon and right kidney cancer. Laparoscopic surgery was performed in cooperation with urologists. A right hemicolectomy was performed first at a lithotomy position. A right radical nephrectomy was then performed after changing to the left lateral position. The operation time was 450 minutes, and the blood loss was 60 ml. Chylous ascites were confirmed, but conservatively improved after surgery. Although synchronous colorectal and kidney cancers have not been confirmed in many cases, it is estimated that such synchronous cancers will increase with the aging of society and development of improved diagnostic imaging techniques. Therefore, simultaneous laparoscopic surgery is a safe and minimally invasive procedure with detailed surgical planning and a sophisticated surgical technique, including ensured port setting and body positioning, in cooperation with urologists.
We herein present the case of a-58-year-old female with a metastasis of breast cancer to the appendix, which caused acute appendicitis. She had undergone a bilateral partial mastectomy with sentinel lymph node biopsy ten years earlier at another hospital. She had subsequently received radiation therapy, chemotherapy and endocrine therapy. There had been no sign of recurrence for five years after the surgical procedure. She was admitted to our hospital because of abdominal pain lately. Abdominal computed tomography showed a dilated and thickened wall of the appendix. She was diagnosed with acute appendicitis and underwent appendectomy. A histopathological examination revealed metastatic breast cancer of the appendix, and the patient received endocrine therapy using an aromatase inhibitor. Metastatic involvement of the appendix should be suspected in any patient with a previous history of breast cancer presenting with acute appendicitis, even if many years have passed after initial therapy.
A 37-year-old male was diagnosed with Fabry disease after renal biopsy. At first, his symptoms were proteinuria and mild kidney dysfunction, but several instances of organ damage, including left ventricular hypertrophy and lacunar brain infarction, opacified lens, and angiokeratoma, were found out after diagnosis. After treatment with alfa-galactosidase A the progression of renal dysfunction was restrained. Because enzyme replacement therapy in Fabry disease might be effective for stabilizing organ functions, it is important to start an early treatment. In the case of male patients who present mild proteinuria, we should pay attention to multiple manifestations.
Recently, immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has the greatest impact on clinical cancer therapy. The rationale for these therapeutic regimens has been established by our advanced knowledge about basic immunology, such as the identification of tumor antigens and the elucidation of self-tolerance mechanisms, and proof-of-concept experiments in animal models. More applications of the immunostimulatory antibodies targeting costimulatory molecules, such as CD40 and CD137, and coinhibitory molecules, such as TIM-3 and VISTA, are now expected. Accumulating evidence shows that these immunostimulatory antibodies can be successfully combined with conventional chemotherapy and radiotherapy to improve their efficacy.
Chagas disease is a zoonotic disease caused by the parasitic protist Trypanosoma cruzi. T. cruzi is transmitted by blood-sucking triatomine insects. Other routes of infection include transfusion, vertical transmission, and contaminated food or drink, such as fresh fruit juice. Chagas disease is only endemic in the Americas, due exclusively to the limited distribution of the insect vectors, whereas a number of patients have been found outside the Americas, particularly among Latin American immigrants. In August 14, 2013, the Japanese Red Cross Society and the Ministry of Health, Labour and Welfare of Japan announced that one blood donor from Latin America had been found to be seropositive for T. cruzi and that blood products prepared from the donated blood had already been delivered to medical institutions. Although later reports denied the occurrence of secondary infection through those blood products, Chagas disease has now become a reality in Japan. Thus, further monitoring and preparedness for Chagas disease are necessary.