Nara-shi, Japan
Nara-shi, Japan

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Hara M.,Yoshida Hospital | Yamagata K.,University of Tsukuba | Tomino Y.,Juntendo University | Saito A.,Niigata University | And 5 more authors.
Diabetologia | Year: 2012

Aims/objective Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Recent studies have demonstrated that podocyte injury is involved in the onset of and progression to renal insufficiency. Here, we describe a novel, highly sensitive ELISA for detecting urinary podocalyxin, a glycoconjugate on the podocyte apical surface that indicates podocyte injury, particularly in the early phase of diabetic nephropathy. Methods Urine samples from patients with glomerular diseases (n=142) and type 2 diabetes (n=71) were used to quantify urinary podocalyxin by ELISA. Urine samples were obtained from 69 healthy controls for whom laboratory data were within normal values. Podocalyxin was detected in urine by immunofluorescence, immunoelectron microscopy and western blotting. Results Morphologically, urinary podocalyxin was present as a vesicular structure; western blotting showed it as a positive band at 165-170 kDa. Levels of urinary podocalyxin were elevated in patients with various glomerular diseases and patients with diabetes. In patients with diabetes, urinary podocalyxin was higher than the cut-off value in 53.8% patients at the normoalbuminuric stage, 64.7% at the microalbuminuric stage and 66.7% at the macroalbuminuric stage. Positive correlations were observed between urinary podocalyxin levels and HbA1c, urinary β2 microglobulin, α1 microglobulin and urinary N-acetyl-β-D-glucosaminidase, although urinary podocalyxin levels were not correlated with other laboratory markers such as blood pressure, lipid level, serum creatinine, estimated GFR or proteinuria. Conclusions/interpretation Urinary podocalyxin may be a useful biomarker for detecting early podocyte injury in patients with diabetes. © The Author(s) 2012.


Ikezumi Y.,Niigata University | Suzuki T.,Niigata University | Yamada T.,Niigata University | Hasegawa H.,Niigata University | And 5 more authors.
Pediatric Nephrology | Year: 2015

Background: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. Methods: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10—a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). Results: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis (p < 0.0001), and kidney function (r =−0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells (r = 0.79, p < 0.01) and parameters of interstitial fibrosis (p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-β1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. Conclusions: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS. © 2014, IPNA.


Yamamoto S.,Niigata University | Mikami N.,Niigata University | Matsuno M.,Yoshida Hospital | Hara T.,Niigata University | And 3 more authors.
Bioscience, Biotechnology and Biochemistry | Year: 2010

The effects of a high-pressure treatment on the IgEspecific binding activity and structural changes to bovine gamma globulin (BGG), a beef allergen, were investigated. The allergenicity of pressure-treated BGG was also evaluated. We found that the IgE-specific binding activity and allergenicity of BGG were decreased by the high-pressure treatment. Almost no significant change in secondary structure was apparent for pressurized BGG, but a change in the tertiary structure was detected. The decreased IgE-specific binding activity and allergenicity of pressurized BGG were probably due to changes in the tertiary structure caused by pressurization. The results of this study suggest that a high-pressure treatment would be an effective food-processing technique to reduce the allergenicity of BGG.


PubMed | Gifu University, Nihon Fukushi University, Midori Hospital and Yoshida Hospital
Type: | Journal: Psychiatry and clinical neurosciences | Year: 2016

Many studies have reported that the prevalence of mental illness and cognitive disability is higher among homeless individuals compared to the general population, and the rates of mental illness among the homeless population have recently increased. This study compared causes of homelessness or barriers to escaping homelessness for people with/without mental illness/cognitive disability, revealed problems with the Japanese homeless policy, and proposed an effective and necessary support system.The participants were 114 homeless individuals. A psychiatric diagnostic interview and the Wechsler Adult Intelligence Scale, version III were used to measure participants mental health and cognitive abilities. A questionnaire was administered comprising 17 items related to the causes of their homelessness and barriers to escaping from it. Participants were divided into four groups: with/without mental illness or cognitive disability, and a Fishers exact test was used to compare the questionnaire results.Individuals with cognitive disabilities considered bad relationships with their family members to be the cause of their homelessness. Conversely, normal individuals considered their homelessness to be the result of debt more so than did individuals with mental problems. Individuals with mental illness had more difficulties escaping homelessness than did either normal individuals or individuals with cognitive disability. This tendency was observed most strongly among individuals with both mental illness and cognitive disability.The difficulties with human relationships hid behind economic problems, which most homeless individuals considered to be the cause of their homelessness. Furthermore, these difficulties were exacerbated among those individuals with mental problems.


Nishio A.,Gifu University | Yamamoto M.,Gifu University | Ueki H.,Gifu University | Watanabe T.,Midori Hospital | And 4 more authors.
Psychiatry and Clinical Neurosciences | Year: 2015

Aim While it has been reported that the prevalence of mental illness is higher in homeless people than in the national population, few studies have investigated the prevalence of intellectual and developmental disability among the homeless. In this study, we conducted a survey to comprehensively assess these mental problems among homeless people in Nagoya, Japan. Methods The subjects were 18 homeless men. Mental illness was diagnosed with semi-structured interviews conducted by psychiatrists. We used the Wechsler Adult Intelligence Scale III to diagnose intellectual disability. Discrepancies between Wechsler Adult Intelligence Scale III subtest scores were used as criteria for developmental disability. Results Eleven of the 18 participants were diagnosed with mental illness: six with mood disorder, two with psychotic disorder, and six with alcohol problems. The mean IQ of all subjects was 83.4?±?27.4. The 95% confidence interval (CI) was 96.2-69.1. Seven participants were found to have intellectual disability. Three men showed discrepancies of more than 10 between subtest scores, and all of them were diagnosed with a mental illness. We divided the participants into four groups: those with mental illness only; those with intellectual disability only; those with both problems; and those without diagnosis. The men with intellectual disability only were significantly younger and had been homeless since a younger age than the other groups. Participants diagnosed with a mental illness had been homeless for longer than those without mental health problems. Conclusion Although the sample size was limited, this study revealed the high prevalence of mental illness and intellectual disability, 61% (95%CI, 35-83%) and 39% (95%CI, 17-64%), respectively, in homeless people in Nagoya, Japan. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.


Hara M.,Yoshida Hospital | Yanagihara T.,Yoshida Hospital | Hirayama Y.,Denka Seiken Co Ltd | Ogasawara S.,Denka Seiken Co Ltd | And 3 more authors.
Human Pathology | Year: 2010

Podocyte injury is involved in both the onset and progression of glomerular diseases. Our previous studies revealed that apical cell membranes of podocyte are shed into urine sediment and that urinary podocalyxin is a useful biomarker of podocyte injury. In this study, we examined the origin of urinary podocalyxin. Urine samples and kidney specimens from healthy children (n = 126) and patients with glomerular diseases (n = 77) were analyzed by immunohistologic methods. Immunofluorescence studies demonstrated that urinary podocalyxin was shed as granular structures into both the urine sediment and supernatant. Large amounts of podocalyxin were shed into both the urine sediment (17.2 ± 3.2 ng/mg creatinine) and the supernatant (172.6 ± 24.6 ng/mg creatinine) of patients, compared with the small amounts of urinary podocalyxin in healthy controls (sediment, 0.5 ± 0.1 ng/mg creatinine; supernatant, 24.3 ± 3.5 ng/mg creatinine). Electron and immunoelectron microscopic examinations showed that podocalyxin-positive vesicles in the sediment (125.6 ± 8.8 nm) and the supernatant (121.2 ± 6.4 nm) were similar in size to podocyte microvilli in biopsy specimens (123.6 ± 8.9 nm), differentiating them from the much smaller urine exosomes (30-80 nm in diameter). Urine podocalyxin-positive vesicles tested negative in immunofluorescence microscopy on both exosomal markers CD24 and CD63. Podocalyxin-positive vesicles also tested negative for cytoskeletal markers, and electron microscopic examination revealed tip vesiculation of microvilli. We conclude that human urinary apical cell membrane vesicles appear to originate not from podocyte exosomes but from tip vesiculation of glomerular podocyte microvilli. © 2010 Elsevier Inc. All rights reserved.


Asao R.,Juntendo University | Asanuma K.,Juntendo University | Kodama F.,Juntendo University | Akiba-Takagi M.,Juntendo University | And 15 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2012

Background and objectives Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN). Design, setting, participants, & measurements Urine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA. Results Histologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P,0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22) (0.49 [interquartile range (IQR), 0.20-0.88] g/g creatinine versus 0.20 [IQR, 0.10-0.33] g/g creatinine; P,0.01). The number of urinary podocytes in patients with segmental sclerosis was higher than in patients without (1.05 [IQR, 0.41-1.67] per mg creatinine versus 0.28 [IQR, 0.10-0.66] per mg creatinine; P,0.01). Conclusions Levels of u-PCX and the number of urinary podocytes are associatedwith histologic abnormalities in adults with IgAN. © 2012 by the American Society of Nephrology.


Kiyomizu K.,Yoshida Hospital | Kiyomizu K.,University of Miyazaki
Equilibrium Research | Year: 2013

We classified psychogenic dizziness into 3 types, such as the narrow type, the wide type and psychiatric comorbidity. Among these, 69.1% (362/524) of our patients with dizziness were diagnosed as having psychiatric comorbidity, and independently in a German facility, similar number of 68.3% (129/189) of patients with dizziness were diagnosed as having psychiatric comorbidity. Therefore, in our hospital, psychological tests are routinely performed on our patients with dizziness. Patients with dizziness of unknown cause (DUC), otogenic vertigo (OV) and Meniere's disease (MD) exhibited a higher prevalence of psychiatric comorbidity (DUC = 73.6%, OV = 69.5%, MD = 70.1%). Of patients with dizziness and psychiatric comorbidity, various types of psychiatric disorders were found, such as anxiety or panic disorders (F41), mood disorders (F3), adjustment disorders or posttraumatic stress disorders (F43), dissociative disorders (F44), other neurotic disorders, organic mental disorders (FO) and schizophrenia (F2). These patients suffering from dizziness were not only treated by otolaryngologists, but also received psychiatric therapy, and 72.9% of these patients were prescribed psychotropic drugs in our hospital. We believe that psychotropic drugs should be prescribed according to the advice given from psychiatrists or the doctors who are familiar with these drugs. Patients with depression often complain of somatic symptoms. In clinical practice 90% of these patients with depression are in general examined by physicians (non-expert psychiatrists) for their primary medical examination. However, it is not easy to distinguish patients with depression from those with bipolar disorder. Recently, serotonin selective re-uptake inhibitors (SSRI) have been prescribed more frequently by physicians, but caution should be exercised in the treatment of patients with depression when physicians prescribe SSRI because these patients may have bipolarity or mild manic symptoms. To reduce the risk of these incidents of misdiagnosis, physicians are strongly encouraged to consider referring these patients with psychiatric disorders to psychiatrists. We believe that collaboration between psychiatrists and physicians in the hospital and/or local doctors can improve the mental condition and the quality of life (QOL) of patients who are suffering from dizziness with psychiatric comorbidity.


Kiyomizu K.,Yoshida Hospital | Kiyomizu K.,University of Miyazaki
Equilibrium Research | Year: 2014

Patients with depression often complain of somatic symptoms like dizziness. It is very difficult to treat patients suffering from severe dizziness and depression with only antivertiginous- drugs. Therefore, using psychotropic drugs is one method to treat this type of patient. However, we believe that psychotropic drugs should be prescribed according to advice from psychiatrists or doctors who are familiar with these drugs, because benzodiazepine drugs can cause drug-dependence, anti-depressants exacerbate the condition in patients with irritability and psychiatric patients are at some risk of suicide. Physicians (nonexpert psychiatrists) need to be careful when treating patients with depression when they prescribe psychotropic drugs, because these patients may become drug-dependent, more irritable and be at some risk of suicide. To reduce the risk of these incidents, physicians are strongly encouraged to consider introducing these patients with psychiatric disorders to psychiatrists. Recently, serotonin selective re-uptake inhibitors (SSRI), another kind of anti-depressant, have been prescribed more frequently by physicians. Our 33-year-old female case with severe dizziness and depression could be completely treated using SSRI. Using SSRI carefully can improve the mental condition and the quality of life (QOL) of patients who are suffering from severe dizziness and depression.


Takagi Y.,Yoshida Hospital
Neuro-Ophthalmology Japan | Year: 2011

Patients with psychosomatic problems are often encountered in daily ophthalmologic practice, including blepharospasm and somatoform disorder. Blepharospasm is often thought to be an undiagnosed disease because of limitations in medical knowledge. The quality of life of patients is notably impaired although their eyeballs are almost normal, but their problems can be alleviated as long as the right diagnosis and treatment are established. Several examples are presented. In ophthalmic practice, many patients with somatoform disorder complain of unexplained symptoms, and psychosomatic medicine is sometimes effective for these patients. Our hospital has not only an ophthalmic ward but also a psychiatric ward, and there are many opportunities to treat patients with psychiatric disorders or dementia. Two such cases are reported. Although it is not easy for medical staff to manage these patients during the perioperative periods of ophthalmic surgery, such operations should be performed without hesitation with the aid of staff from several departments in order to try to improve both their psychotic disorders and their vision.

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