Biomedical subjects

Hiroyasu Yamamoto

Publications and source records attributed to Hiroyasu Yamamoto.

31 records · Page 2Linked to original sources

PubMed2003

Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2.

Salt-inducible kinase (SIK), first cloned from the adrenal glands of rats fed a high salt diet, is a serine/threonine protein kinase belonging to an AMP-activated protein kinase family. Induced in Y1 cells at an early stage of ACTH stimulation, it regulated the initial steps of steroidogenesis. Here we report the identification of its isoform SIK2. When a green fluorescent protein-fused SIK2 was expressed in 3T3-L1 preadipocytes, it was mostly present in the cytoplasm. When coexpressed in cAMP-responsive element-reporter assay systems, SIK2 could repress the cAMP-responsive element-dependent transcription, although the degree of repression seemed weaker than that by SIK1. SIK2 was specifically expressed in adipose tissues. When 3T3-L1 cells were treated with the adipose differentiation mixture, SIK2 mRNA was induced within 1 h, the time of induction almost coinciding with that of c/EBPbeta mRNA. Coexpressed with human insulin receptor substrate-1 (IRS-1) in COS cells, SIK2 could phosphorylate Ser(794) of human IRS-1. Adenovirus-mediated overexpression of SIK2 in adipocytes elevated the level of phosphorylation at Ser(789), the mouse equivalent of human Ser(794). Moreover, the activity and content of SIK2 were elevated in white adipose tissues of db/db diabetic mice. These results suggest that highly expressed SIK2 in insulin-stimulated adipocytes phosphorylates Ser(794) of IRS-1 and, as a result, might modulate the efficiency of insulin signal transduction, eventually causing the insulin resistance in diabetic animals.

3T3 Cells↗

PubMed2003

Surgical verification of percutaneous maxacalcitol injection therapy on enlarged parathyroid glands in chronic dialysis patients.

Selective percutaneous ethanol injection therapy (PEIT) has been used to control parathyroid function in patients with secondary hyperparathyroidism (2HPT) when one or more parathyroid gland (PTG) progresses to the nodular hyperplasia stage. However, PEIT can have adverse side effects, such as nerve paralysis and adhesion, because the ethanol is destructive. Intraparathyroid injection of a vitamin D analogue has been designed as a treatment to control parathyroid function without destruction of the PTG or causing adhesions to the surrounding tissue, and the present study aimed to verify the effect of percutaneous maxacalcitol (22-oxacalcitriol) as the vitamin D analogue. The study group comprised two haemodialysis patients who needed parathyroidectomy for uncontrolled 2HPT with a maximal PTG diameter >20 mm. The treatment began with an ultrasonographically guided injection of 10 microg of maxacalcitol solution into the largest PTG and, 1 week later, parathyroidectomy was performed to examine the effect of the maxacalcitol injection both macroscopically and microscopically. The injected glands were swollen and inflamed, and adhesions made it difficult to remove them. There was macroscopic and microscopic evidence of haemorrhagic necrosis and adhesions to the surrounding tissue. Direct vitamin D analogue injection should not be performed as a primary treatment option because the adverse side effects are not overcome by this technique.

Calcitriol↗

PubMed2003

IRMA (whole PTH) is a more useful assay for the effect of PTH on bone than the Allegro intact PTH assay in CAPD patients with low bone turnover marker.

The common intact parathyroid hormone (i-PTH) assay detects not only PTH (1-84) but also the PTH (7-84) fragment. Recently, it was reported that the PTH (7-84) fragment is an antagonist to the biological action of PTH (1-84). It was also reported that the accumulation of the PTH (7-84) fragment plays a role in skeletal resistance in haemodialysis (HD) patients. However, the role of accumulation of the PTH (7-84) fragment in continuous ambulatory peritoneal dialysis (CAPD) patients, with a different clearance rate from that of HD patients, is still unclear. Therefore, we have measured only the active form of PTH (1-84) using a new method of whole PTH (w-PTH) assay in 20 CAPD patients (15 male and five female; mean age 51.0+/-13.0 years). The mean w-PTH value was 88.5 +/-14.2 pg/ml in CAPD patients, which was 42.1% of i-PTH (152.6+/-23.6 pg/ml). The approximate value of w-PTH was calculated using the following formula (w-PTH=0.58 x iPTH-0.4, R(2)=0.94). PTH (7-84) fragment was calculated by the formula i-PTH-w-PTH. The PTH (7-84) fragment/w-PTH ratio as an index of skeletal resistance, and serum alkaline phosphatase activity as an osteoblastic marker were negatively correlated (P=0.02). From these results, we concluded that the i-PTH level as calculated using the common assay method might lead to an overestimation of parathyroid function and bone turnover in CAPD patients similarly to HD patients. The w-PTH assay may be useful for more precise evaluation of PTH activity in end-stage renal disease patients.

Adult↗

PubMed2002

Reduced IRS-2 and GLUT4 expression in PPARgamma2-induced adipocytes derived from C/EBPbeta and C/EBPdelta-deficient mouse embryonic fibroblasts.

In adipose tissue, the ability of cells to respond to insulin and to express genes such as those encoding fatty-acid-binding protein (422/aP2), lipoprotein lipase (LPL), adipsin and glucose transporter 4 (GLUT4) is acquired during their differentiation into mature adipocytes. It has been recognized that peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding proteins (C/EBPs) play critical roles in adipocyte differentiation. However, it remained uncertain whether PPARgamma or which C/EBP is involved in the acquisition of these characteristics. We introduced PPARgamma2 into C/EBPbeta/delta-double deficient mouse embryonic fibroblasts (MEFs), followed by stimulation with its ligands, in order to define the roles of C/EBPbeta and C/EBPdelta in phenotypic acquisition during adipocyte differentiation. This procedure resulted in differentiation of these MEFs into mature adipocytes morphologically similar to wild-type MEFs. However, the adipocytes derived from the C/EBPbeta/delta-deficient MEFs showed lower expression of GLUT4 and adipsin mRNA than those derived from wild-type MEFs, although aP2 and LPL mRNA levels were similar in both types. The C/EBPbeta/delta-deficient adipocytes also expressed lower amounts of insulin receptor substrate 2 (IRS-2) than the adipocytes derived from wild-type MEFs, whereas the amounts of insulin receptor and IRS-1 were similar. Finally, insulin-responsive 2-deoxyglucose uptake was lower in the C/EBPbeta/delta-deficient cells. It could thus be demonstrated that C/EBPbeta and C/EBPdelta are involved in the acquisition of IRS-2 and GLUT4 expression as well as in insulin-sensitive glucose uptake during adipocyte differentiation.

Adipocytes↗

PubMed2002

The negative Ca(2+) balance is involved in the stimulation of PTH secretion.

The low calcium (Ca(2+)) dialysate have been developed to diminish the risk of hypercalcemia with the administration of active vitamin D and Ca(2+) carbonate as phosphate binder. Today, increasing numbers of hemodialysis (HD) patients have been on the low Ca(2+) dialysate (Ca(2+) = 2.5 mEq/l). However, the clinical consequences of a negative calcium net-balance which may be induced by the use of low Ca dialysate are not well evaluated. In the present study, we explored the effects of low Ca(2+) dialysate on the calcium balance and the PTH secretion. Eighty one chronic HD patients (male/female: 47/34; mean age: 60.2 +/- 1.5 years; mean HD periods: 11.1 +/- 0.8 years) who had been dialyzed with 3.0 mEq/l Ca(2+) dialysate were studied. All patients were transferred to the low Ca dialysate, which actually brought about a negative net-balance in Ca (mean: -94.5 mg) and an increase in serum intact PTH levels (mean: +23.7%: p = 0.03) during a single HD session. However, no changes in serum ionized Ca(2+) were found in spite of negative Ca(2+) balance. One month after change to the low Ca(2+) dialysate (total 12 sessions in each case), serum intact PTH levels increased significantly (186.7 +/- 19.5 vs. 216.2 +/- 21.9 pg/ml: p = 0.01) in spite of the fact that no changes were found in serum ionized Ca(2+), Pi and Mg. This result indicates that the negative Ca(2+) balance during low-Ca(2+) hemodialysis-stimulated PTH secretion, which offset the decrease of serum Ca(2+); a trade-off phenomenon between negative Ca balance and PTH. This suggests that low Ca(2+) dialysate may exaggerate the progression of secondary hyperparathyroidism.

Calcium↗

PubMed2002

Isolated adrenocorticotropin deficiency presenting with impaired renin-angiotensin-aldosterone system and suppressed parathyroid hormone-vitamin D axis.

We report here a 47-year-old woman with isolated adrenocorticotropin (ACTH) deficiency (IAD). She presented impaired renin-angiotensin-aldosterone (R-A-A) system and suppressed parathyroid hormone (PTH)-vitamin D system. She showed severe hyponatremia due to secondary adrenocortical insufficiency, which was deteriorated by hypoaldosteronism. She also showed hyperphosphatemia and relative hypercalcemia with suppressed PTH-vitamin D axis. Moreover, she showed hypothyroidism, which was thought to be important to maintain normal Ca levels under secondary hypoadrenalism via decrease in bone resorption by T3. Replacement with glucocorticoid completely normalized PTH-vitamin D axis and R-A-A system. Thus, the present case implicates that severe adrenocortical deficiency due to IAD might affect both R-A-A system and PTH-vitamin D axis. These findings suggest that the ACTH-cortisol axis has an important role in mineral metabolism in vivo.

Adrenocorticotropic Hormone↗

PubMed2002

[Long-standing high-transport membrane as a risk factor for EPS development after PD withdrawal: an analysis based on changes in peritoneal function during and after CAPD withdrawal].

The pathophysiology of encapsulating peritoneal sclerosis (EPS) that develops after withdrawal from long-standing dependence on CAPD remains unclear. The aim of this study was to clarify the risk factors for EPS as expressed in the peritoneal function. Fourteen patients who had shifted to standard hemodialysis after long-term CAPD (average, 105 months) were studied: 3 developed EPS after PD withdrawal while 11 did not. Analysis of the data obtained from the peritoneal equilibration test (PET) revealed that: (1) the dialysate/plasma creatinine ratio (D/Pcr) was significantly higher in the EPS group than in the non-EPS group during the course of PD as well as after PD withdrawal; and (2) eight patients, including the 3 with EPS, were classified as being in a high-transport membrane state (HTS) at PD withdrawal. The duration of HTS during PD was longer in those patients with EPS. During the periods after PD withdrawal, none of these EPS patients recovered from HTS, whereas 4 of the 5 non-EPS patients did. These data suggest that long-standing HTS during the course of PD as well as post-withdrawal, may be risk factors for EPS development. For this reason, it is indicated that PET has clinical relevance in examining sequential changes in peritoneal function and in detecting those patients at risk of EPS.

Adult↗

PubMed2002

High-transport membrane is a risk factor for encapsulating peritoneal sclerosis developing after long-term continuous ambulatory peritoneal dialysis treatment.

Increased peritoneal function has been suggested to be a risk factor for developing encapsulating peritoneal sclerosis (EPS); however, clinical evidence is scarce. The present study aimed to clarify the specific character of peritoneal function in patients who developed EPS after withdrawal from peritoneal dialysis (PD). We studied 12 patients who developed EPS after PD withdrawal [(EPS group) mean PD duration: 109 months; mean period of EPS development: 7.0 months after withdrawal] and 128 patients who did not develop EPS (non EPS group). All 140 patients were withdrawn from continuous ambulatory peritoneal dialysis (CAPD) and were observed for the following 24 months. Based on the records of the annual peritoneal equilibration tests (PETs), we analyzed (1) the patients' dialysate-to-plasma (D/P) creatinine at various durations on PD, and (2) the accumulative appearance incidence of high-transport (HT) state of peritoneal membrane. The mean D/P creatinine in EPS group was significantly higher than that in the non EPS group in the course of PD from the 6th to the 10th year. The accumulative incidence of HT was significantly higher in the EPS group than in the non EPS group, indicating early development of HT membrane in EPS group. Early development of increased D/P creatinine, classified as HT state, was observed during certain periods on PD in patients who developed EPS after PD withdrawal. That finding may indicate that HT state of peritoneal membrane is an early marker for EPS, and that the PET is useful to detect patients at high risk of EPS.

Adult↗

PubMed2002

Fifteen cases of encapsulating peritoneal sclerosis related to peritoneal dialysis: a single-center experience in Japan.

To evaluate the incidence and characteristics of encapsulating peritoneal sclerosis (EPS), we analyzed 111 patients who had been transferred to hemodialysis and had been periodically monitored using the peritoneal equilibration test. Encapsulating peritoneal sclerosis was diagnosed in 11 patients. All patients had high-transport peritoneum, and 10 patients had been treated with continuous ambulatory peritoneal dialysis (CAPD) for more than 72 months. Incidence of EPS increased according to prolongation of CAPD. To evaluate outcome, we analyzed 15 cases of EPS. All patients were treated with total parenteral nutrition (TPN). Five patients improved with TPN alone. However, the remaining 10 patients showed deterioration. Of those 10, 4 patients died. They had not been treated with corticosteroids (CSs). The remaining 6 patients were treated with CSs, but they did not improve. Those cases required surgical treatment. The postoperative course in 4 patients was satisfactory, but 2 patients died. In our center, the EPS survival rate was 60%. In patients treated with TPN alone, the remission rate was only 33.3%. Administration of CSs could not improve that rate. In 6 patients treated with surgery, the mortality rate was 33.3%. When EPS symptoms are not ameliorated by CS and TPN, surgical treatment should be considered. To prevent EPS, high-risk patients who have more than 72 months on CAPD and who have a high-transport peritoneum should discontinue CAPD.

Biological Transport↗

PubMed2002

Risk factors and preventive measures for encapsulating peritoneal sclerosis--Jikei experience 2002.

A growing incidence of encapsulating peritoneal sclerosis (EPS) has been reported recently in Japan, and it is now urgent to establish preventive measures against EPS development. In the present paper, we describe our observational results regarding the risk of EPS development and the characteristic features of patients with EPS, in terms of peritoneal morphology and peritoneal function as determined by peritoneal equilibration test. The ongoing working protocol for EPS prevention at Jikei University Hospital is also discussed. Our findings have revealed that long-term continuous ambulatory peritoneal dialysis (CAPD) is a risk factor for EPS development after transfer to hemodialysis from peritoneal dialysis (PD), and that, in most patients with EPS, peritoneal function is characterized by a longstanding high-transport state. The striking alterations in peritoneal morphology between patients with EPS and those with simple long-term CAPD hyperplasia include, in EPS patients, a prominent thickening of the collagenous layer of the peritoneum with neoangiogenesis and myofibroblastic transformation. Based on our findings, we established a withdrawal protocol for long-term CAPD patients, with the goal of preventing EPS. Those who have been on PD treatment for more than 72 months with high-transport state are candidates for withdrawal from PD, with performance of peritoneal lavage thereafter for a certain period of time. The clinical benefit of post-PD lavage has not yet been determined; however, the maneuver could be precluded in patients at low risk of EPS, because it was found that some patients can recover to average transport state during the period of PD withdrawal. Patients who remain high transporters with inflammatory reaction might require pharmacologic intervention, including prednisolone therapy. Further observations are required to validate our approach.

Adult↗

PubMed2002

[Effect of angiotensin II receptor antagonist (losartan) on renal function, serum potassium and blood pressure in patients with advanced renal failure: differences between patients with a serum creatinine (SCr) level higher than 3 mg/dl and those with a lower SCr level].

The administration of angiotensin II receptor antagonist(AIIA) to patients with advanced chronic renal failure(CRF) is not actively recommended. This study was performed to verify the appropriateness of this situation and to determine if there are any substantial differences between patients with a serum creatinine(SCr) level higher than 3 mg/dl and those with a lower SCr level in terms of the clinical effects such as renal function, serum potassium level and systemic blood pressure(BP) after the administration of AIIA. Sixteen patients with advanced CRF who were admitted to the out-patient clinic in Jikei University Hospital(1998/1-1999/12) were enrolled(average age: 65 years, underlying renal disease: diabetic nephropathy 6, CGN 5, and other 1). They had never been administered AIIA before. The patients were classified into two groups in accordance with their level of SCr: group A(SCr lower than 3.0 mg/dl; n = 11), and Group B(SCr higher than 3.0 mg/dl; n = 5). Losartan(50 mg/day) administration was started in order to examine parameters such as the SCr, potassium, BP at the out-patient clinic, and urinary protein excretion at the 0, 1, 3, 6, 9, and 12 month time points. Although the 1/SCr values provided negative slopes with time in both groups, no significant difference was found between the two slopes. There were no changes in the serum potassium levels or urinary protein excretion during the study period in either group, and no statistical difference was found between the two groups. Although the serum potassium level exceeded 5.5 mEq/l in two patients each in both groups, the level was controlled by diet therapy with restricted potassium. BP was reduced significantly in both groups during the study period, and no statistical difference in BP reduction was observed between the two groups. In conclusion, the results indicate there were no differences in the effect on renal function, serum potassium levels or systemic BP between the patients with a SCr level higher than 3.0 mg/dl and those with a lower level. The results also support the notion that patients with advanced renal dysfunction are not precluded from AIIA administration.

Aged↗

PubMed2001

Hepatoma-derived growth factor stimulates cell growth after translocation to the nucleus by nuclear localization signals.

Hepatoma-derived growth factor (HDGF) is the original member of the HDGF family of proteins, which contains a well-conserved N-terminal amino acid sequence (homologous to the amino terminus of HDGF; hath) and nuclear localization signals (NLSs) in gene-specific regions other than the hath region. In addition to a bipartite NLS in a gene-specific region, an NLS-like sequence is also found in the hath region. In cells expressing green fluorescence protein (GFP)-HDGF, green fluorescence was observed in the nucleus, whereas it was detected in the cytoplasm of cells expressing GFP-HDGF with both NLSs mutated or deleted. GFP-hath protein (GFP-HATH) was distributed mainly in the nucleus, although some was present in the cytoplasm, whereas GFP-HDGF with a deleted hath region (HDGFnonHATH) was found only in the nucleus. Exogenously supplied GFP-HDGF was internalized and translocated to the nucleus. GFP-HATH was internalized, whereas GFP-HDGFnonHATH was not. Overexpression of HDGF stimulated DNA synthesis and cellular proliferation, although HDGF with both NLSs deleted did not. Overexpression of HDGFnonHATH caused a significant stimulation of DNA synthesis, whereas that of hath protein did not. HDGF containing the NLS sequence of p53 instead of the bipartite NLS did not stimulate DNA synthesis, and truncated forms without the C- or N-terminal side of NLS2 did not. These findings suggest that the gene-specific region, at least the bipartite NLS sequence and the N- and C-terminal neighboring portions, is essential for the mitogenic activity of HDGF after nuclear translocation.

3T3 Cells↗

PubMedDate not supplied

The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells.

Endothelial dysfunction is a phenomenon often observed in diabetic patients, which is a cause for vascular complications of diabetes mellitus. Endothelium-derived nitric oxide (NO) is responsible for vasodilatation, and NO-dependent vasodilatation is diminished in diabetic patients. In the present study, we evaluated the effects of thiazolidinediones (TZDs), antidiabetic drugs known to improve insulin resistance and to have vasodilating properties, on endothelial NO synthase (eNOS) expression in cultured vascular endothelial cells. Human umbilical vein endothelial cells were treated with the TZDs troglitazone and pioglitazone, or the peroxisome proliferator-activated receptor (PPAR) gamma activator 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-dPGJ2). The expression of eNOS protein and its mRNA was determined by Western and Northern blot analyses, respectively. The effect of alpha-tocopherol that possesses structural similarity to troglitazone was also examined. Troglitazone up-regulated eNOS protein and its mRNA levels, whereas pioglitazone and 15-dPGJ2 failed to increase their levels. By contrast, alpha-tocopherol also increased in eNOS protein and mRNA. These results suggest that troglitazone up-regulates eNOS expression probably through its 6-hydroxychromanes structure but not activating PPARgamma.

Analysis of Variance↗