Naoyuki Yamamoto

Tokai University, Hiratuka, Kanagawa, Japan

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Publications (15)10.84 Total impact

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    ABSTRACT: A 73-year-old male with diabetes mellitus had been treated with insulin for six years. He developed a solid mass on his left lateral of the abdomen at the insulin injection site. A firm subcutaneous mass with dark-red erythema was overlaid by dark-brown keratinized plaques. On histological examination of the mass, keratin proliferation and epidermal papilloma were observed. There were four previously reported cases of acanthosis nigricans that were considered to be caused by continuous injections of insulin. Using immunohistochemistry, in our case the findings were positive in the basal epithelial and prickle cell layers when the patient's lesion was dyed with insulin-like growth factor (IGF)-1 antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found in our patient has not been reported previously, to our knowledge.
    The Tokai journal of experimental and clinical medicine 01/2014; 39(1):5-9.
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    ABSTRACT: Objective To evaluate the effects of six-month liraglutide treatment on body weight, visceral and subcutaneous fat and related markers in Japanese type 2 diabetic patients. Methods A total of 59 patients with type 2 diabetes were treated with liraglutide (0.3 mg/day for ≥1 week and then 0.6 mg/day for ≥1 week, gradually increasing the dose to 0.9 mg/day) for six months. Changes in body weight, body mass index (BMI), HbA1c, the fasting blood glucose level, visceral and subcutaneous fat areas, hepatic and renal CT values and the associated markers proinsulin, adiponectin and pentraxin (PTX) 3 were measured. Results The study included one treatment-naïve patient, 10 patients who were switched from oral antidiabetic drugs and 35 patients who were switched from insulin therapy. At six months after treatment, the preprandial blood glucose levels were higher (148.8±40.5 mg/dL) than the baseline values (130.8±36.7, p<0.05); however, body weight, BMI and abdominal circumference were lower, and the liver/kidney CT ratio improved significantly from 1.64±0.44 at baseline to 1.78±0.42. An analysis of the patients who were not pretreated with insulin resistance ameliorators showed that six months of liraglutide treatment significantly decreased the subcutaneous but not visceral fat areas, significantly decreased the serum adiponectin levels and significantly increased the serum PTX3 levels. Conclusion In addition to its glucose-lowering effects, liraglutide exhibits weight loss promotion actions, reducing subcutaneous fat areas in particular. The weight and total fat area reduction properties of liraglutide are likely to be beneficial when this medication is used in combination with other oral antidiabetic drugs and insulin.
    Internal Medicine 01/2013; 52(10):1029-34. · 0.97 Impact Factor
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    ABSTRACT: Background: Diabetic patients on hemodialysis often experience severe hypoglycemia during intensive insulin therapy using conventional neutral protamine hagedorn (NPH) or nonintensive therapy with premixed insulin. Insulin glargine can simulate normal basal insulin secretion. We investigated the efficacy and safety of switching from NPH to glargine in type 2 diabetes patients on hemodialysis. Methods: Hemodialysis patients who were being treated with NPH-based basal-bolus insulin therapy, regular insulin, NPH insulin or premixed insulin were switched to glargine. The target early morning fasting blood glucose (FBG) level was 110 mg/dL. Any increase in glargine dose was coupled with a reduction in the dose of any regular or rapid-acting insulin analogue as far as possible while maintaining a constant daily insulin dose. FBG, HbA1c, daily insulin dosage, percentage of basal insulin dose in total daily insulin dose, body weight and incidence of hypoglycemic events were evaluated during the study period. Quality of life (QOL) was measured with a short questionnaire. Results: HbA1c improved significantly during the observation period after switching. The daily insulin dose was reduced from 20.1 ± 15.2 to 18.1 ± 15.1 U/day, although the change was not statistically significant. FBG decreased significantly from 174.4 ± 58.7 to 126.2 ± 27.7 mg/dL. Body weight measured after dialysis did not change, and there were no changes in hemoglobin or hematocrit. The frequency of hypoglycemic episodes decreased significantly. QOL reports with switching to glargine were improved compared with those before switching. Conclusion: The results suggest that glargine is useful, can improve QOL of diabetic patients on hemodialysis, and achieve better glycemic control than NPH.
    Journal of nephrology 02/2012; · 2.02 Impact Factor
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    ABSTRACT: Attempts to achieve strict glycemic control with basal-bolus insulin therapy required increased dosages of neutral protamine Hagedorn (NPH) insulin. However, high dosage of NPH insulin often occurs nocturnal hypoglycemia. Insulin glargine can simulate normal basal insulin secretion with its flat time-action profiles. To confirm the efficacy of insulin glargine we investigated the type 2 diabetic patients on basal-bolus insulin therapy whose basal insulin was switched from NPH insulin to insulin glargine. The Japanese 400 patients with type 2 diabetes on basal-bolus insulin therapy whose basal insulin was switched from NPH insulin to insulin glargine were followed-up. After the switching, the basal insulin was increased with reference to the self-monitoring of blood glucose results, with the aim of maintaining fasting blood sugar (FBS) level at 110 mg/dL, and simultaneously reducing the bolus insulin dosage to maintain the total daily insulin dosage. We were able to lower FBS significantly with almost no serious hypoglycemia. HbA1c also improved significantly. The improvements in FBS and HbA1c levels did not require a significant increase in the total insulin dosage. Our results suggest that basal insulin supplementation using insulin glargine is a useful method to control not only FBS but also HbA1c.
    The Tokai journal of experimental and clinical medicine 01/2012; 37(2):35-40.
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    ABSTRACT: To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes. We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose. Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides). BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic β cells may increase its effectiveness.
    The Tokai journal of experimental and clinical medicine 01/2012; 37(2):41-6.
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    ABSTRACT: Tubulointerstitial fibrosis (TIF) is seen as the final stage of progressive nephropathy, and the degree of TIF is reported to be a major determinant in renal outcomes. In recent years, epithelial-mesenchymal transition (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each been implicated in the mechanism of TIF. The relationship between EMT and these transcription factors is unclear, however, so in this study we attempted to elucidate the correlation between the expression of Snai1 and clinical markers. We performed immunohistochemical staining on human renal tissue obtained from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double positive tubular epithelial cells. Snai1 protein was mainly observed in the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular epithelial cells also contained Snai1-positive nuclei, and double positive cell numbers were increased in IgAN and DN. Statistical analysis revealed positive correlations between Snai1/vimentin double positive cell numbers and proteinuria and creatinine in IgAN. Positive correlations were also seen between Snai1/vimentin double positive cell numbers and the severity of proteinuria in DN. The results of this study indicate that Snai1 plays an important role in TIF in patients with progressive nephropathy.
    Journal of nephrology 06/2011; 25(2):233-9. · 2.02 Impact Factor
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    ABSTRACT: Diabetic nephropathy (DN) is a common cause of end-stage renal disease. However, the precise mechanism of DN, which involves the role of lipid, is still not fully understood. Lectin-like oxidized LDL receptor-1 (LOX-1) is a type II single-transmembrane protein that binds oxidized low density lipoprotein (Ox-LDL). This study examined the expression of LOX-1 mRNA in renal tissues from type 2 diabetes patients with DN using in situ hybridization (ISH). Renal tissues were obtained from 15 type 2 patients with DN and 5 minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN) and normal human kidney (NHK). Glomerular and tubulointerstitial LOX-1 mRNA expression was evaluated by ISH. Results The cells positive for LOX-1 mRNA were identified in the glomeruli of DN, MCNS, MN and NHK, however, there was no positive signal in the tubulointerstitial area in MCNS and NHK. Some cells positive for LOX-1 mRNA were detectable in the tubulointerstitial area in DN and MN. In the results of glomerular staining, there was no significant difference between them. There was a significant correlation between the tubulointerstitial LOX-1 expression and the degree of the tubulointerstitial damage and urinary protein in DN. Increased expression of LOX-1 mRNA in the tubulointerstitial area may be closely linked to the development and progression of human DN, and in particular the tubulointerstitial damage.
    Internal Medicine 02/2009; 48(4):189-94. · 0.97 Impact Factor
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    ABSTRACT: The loss of podocytes has been reported to have a role in the onset and progression of diabetic nephropathy (DN). Although structural changes such as podocyte hypertrophy are considered to be associated with podocyte loss, the relationship has not been thoroughly investigated using human DN renal tissues. The subjects were 17 patients with DN diagnosed histopathologically by renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1 (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the number of podocytes and assess podocyte hypertrophy. The number of podocytes was decreased in DN patients compared with the controls. An inverse correlation was observed between the number of podocytes and both the urinary protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was also more marked in DN patients compared with controls. Based on these results, podocyte loss and hypertrophy were suggested to be involved in the development and progression of human DN.
    Internal Medicine 01/2009; 48(18):1615-20. · 0.97 Impact Factor
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    ABSTRACT: Alpha-actinin-4 is an actin filament crosslinking protein that interacts with intercellular adhesion molecules. Recent animal studies suggested that alpha-actinin-4 is an essential component of the glomerular filtration barrier. However, little is known about its expression in human diabetic nephropathy (DN). Renal biopsy tissues were obtained from 17 patients with DN. We determined the mRNA and protein expression levels of alpha-actinin-4 by in situ hybridization and immunohistochemistry. The histopathological severity of DN was classified into two groups: mild and moderate mesangial expansion groups. We also measured urinary protein excretion and creatinine clearance. Podocytes were positively stained for alpha-actinin-4 mRNA and protein. In the glomeruli, the percentage of cells positive for alpha-actinin-4 mRNA was significantly lower in moderate mesangial expansion group than in mild mesangial expansion group and control. The percentage of immunohistochemically positive area for alpha-actinin-4 protein in moderate mesangial expansion group was significantly lower than in mild mesangial expansion group and control. The percentage of cells positive for alpha-actinin-4 mRNA and area positive for the protein correlated inversely with severity of proteinuria. Our results suggest that low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human DN.
    Internal Medicine 02/2008; 47(12):1099-106. · 0.97 Impact Factor
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    ABSTRACT: To determine the clinical usefulness of long-term intensive insulin therapy in Japanese patients with type 2 diabetes. Various clinical indicators and potential of withdrawal from insulin therapy were investigated in 20 type 2 diabetic patients receiving treatment in the outpatient clinic over a period of 8 years after starting intensive insulin therapy between April 1997 and March 1999. The mean glycated hemoglobin (HbA1c) was approximately 6.5%, and there was no significant increase in insulin dose over a period of 8 years after commencement of intensive insulin therapy. Withdrawal from insulin therapy could be sustained in previously untreated patients. Our results indicated the clinical usefulness of intensive insulin therapy over the long term in Japanese patients with type 2 diabetes and that such therapy could be especially useful for previously untreated patients.
    Internal Medicine 02/2008; 47(24):2109-15. · 0.97 Impact Factor
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    ABSTRACT: We investigated the clinical characteristics of intensive insulin therapy in Japanese type 2 diabetes patients who commenced intensive insulin therapy during the in-hospital diabetes education program at Tokai university hospital. 81 type 2 diabetes patients who received intensive insulin therapy and in-hospital diabetes education program were examined their clinical features. Intensive insulin therapy maintained HbA(1C) below 7% at all time points during the 2-year follow-up, though it was not necessary to increase the insulin dose, thus highlighting the clinical utility of the therapy in preventing diabetic complications. Insulin therapy could be withdrawn from more than 25% of patients. The diabetic morbid period was shorter and urinary C-peptide level at admission was higher in patients of the withdrawal group than those of the non-withdrawal group, suggesting that patients with well maintained pancreatic β cell reserve could be withdrawn from insulin therapy. Based on our results of the efficacy of strict glycemic control for preventing the development and progression of diabetic complications, we recommend early introduction of intensive insulin therapy to achieve better glycemic control.
    The Tokai journal of experimental and clinical medicine 01/2008; 33(2):95-9.
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    ABSTRACT: Membranous nephropathy (MN) is the most common cause of adult-onset nephrotic syndrome and its management is still controversial. The aim of this study was to determine the effectiveness of corticosteroid-alone therapy for controlling proteinuria in MN. Twenty-three patients, which had moderate proteinuria (admission 24-hour urinary protein excretion 1.0 to 3.5 g/day) with primary MN were studied retrospectively. Thirteen patients received corticosteroid-alone therapy combined with rest and dietary therapy (steroid group), while the other 10 patients were treated with rest and diet alone (non-steroid group). These two groups did not differ with respect to their laboratory features at the time of admission. After discharge, 5 of 13 patients of the steroid group dropped out . Therefore, only 8 patients could be followed up. As the result, 5 of 8 patients (62.5%) achieved complete remission (CR) and 3 of 8 patients (37.5%) had incomplete remission (ICR), so none of the patients failed to improve. On the other hand, 3 of 10 patients of the non-steroid group dropped out. Then, 7 patients were followed up. None of the 7 patients showed improvement during follow-up and 5 of these 7 patients were started on corticosteroids. Finally, as this result, 4 of 5 patients (80%) could achieve CR by 2 years after hospital discharge. Moreover, in the remaining 2 patients from the non-steroid group, no remission could be achieved even 2 years after discharge. These results suggest that long-term corticosteroid-alone therapy is beneficial for controlling proteinuria in patients with MN.
    Internal Medicine 02/2007; 46(19):1641-5. · 0.97 Impact Factor
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    ABSTRACT: The receptor for advanced glycation end-products (RAGE) is one of several advanced glycation end-product (AGE)-specific cellular receptors. To evaluate the relationship between AGE and RAGE in renal tissues of diabetic nephropathy (DN), we examined the levels of expression of AGE protein and of RAGE mRNA. We also investigated the relationships among the degree of mesangial expansion and the expression of AGE and RAGE mRNA. Renal biopsy tissues were obtained from 20 patients with DN. We performed immunohistochemical staining using monoclonal anti-AGE antibody and in situ hybridization using non-radioactive oligonucleotide RAGE probe on these tissues. We also examined five control renal samples. We evaluated the intensity of positive anti-AGE antibody staining and the percentage of cells positive for RAGE mRNA. We also measured the total glomerular area and mesangial area in glomeruli using an automatic image analyzer. We then calculated the percentage of mesangial area as a proportion of the total glomerular area (%Mes). Anti-AGE antibody was detected in the expanded mesangial matrix in DN but not in control samples. RAGE mRNA expression was detected mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells, in both DN and control. %Mes correlated significantly with both the intensity of anti-AGE antibody positive staining and the percentage of cells positive for RAGE mRNA. Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.
    Internal Medicine 02/2006; 45(7):435-41. · 0.97 Impact Factor
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    ABSTRACT: We experienced a case of rheumatoid arthritis with nephrotic syndrome. A renal biopsy specimen from this patient showed various renal histological changes. The patient was a 50-year-old man who was diagnosed as having rheumatoid arthritis in 1987. We performed a renal biopsy because he had persistent proteinuria from March in 2002. The renal biopsy specimen showed amyloid AA and P protein deposition in the glomeruli. Moreover mild mesangial proliferation was recognized. IgA-deposition in the mesangial area, and granular-deposition of IgG along the glomerular capillary wall were also observed. In electron microscopy, electron dense deposits were recognized in the mesangial area and subepithelium of the glomerular basement membrane. From these findings, we diagnosed amyloid nephropathy, IgA nephritis and membranous nephropathy. Renal biopsy of patients with RA is useful not only for precise diagnosis, but also for selection of the appropriate treatment.
    Nippon Jinzo Gakkai shi 02/2006; 48(2):67-73.
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    ABSTRACT: Minimal change nephrotic syndrome(MCNS) typically shows no abnormalities in light microscopy. However, there are some minor light microscopic abnormalities that are considered to be MCNS variants. In pediatric nephrology, some researchers have reported that IgM deposition in the mesangium and mesangial hypercellularity are related to the response to steroid therapy and the long-term course. However, it is not clear whether IgM deposition in the mesangium and mesangial hypercellularity is responsible for the clinical course or the steroid response of patients with adult MCNS. To investigate the clinical importance of IgM deposition in the mesangium and mesangial hypercellularity, clinical records, follow up data, and renal samples of 47 patients with MCNS were reviewed. We also compared the histological data with those of a normal control group (n = 5). In our study, the presence of mesangial IgM deposition did not predict the patient's clinical course or responsiveness to steroid therapy. Increase in the number of nuclei in the glomeruli and PAS-positive area also did not correlate with the clinical course or responsiveness to steroid therapy. The data suggest that mesangial IgM deposits and increased mesangial cellularity in adult MCNS may not predict the clinical course or steroid response. However, we investigated only 47 samples in this study, therefore, further studies are necessary to identify the importance of IgM deposition in the mesangium and mesangial hypercellularity in adult MCNS.
    Nippon Jinzo Gakkai shi 02/2006; 48(1):14-21.