Biomedical subjects
Jiro Nakamura
Publications and source records attributed to Jiro Nakamura.
[Pupillary dysfunction in diabetes mellitus].
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Complement activation products in the urine from proteinuric patients.
The presence of plasma proteins in the tubular lumen has variety of adverse effects on the tubular cells. Among various plasma proteins filtered through glomerular barrier, complement has been proven as the possible candidate inducing tubulointerstitial injury. To study the role of intratubular complement activation in proteinuric patients, complement activation products (CAP) at C3 level (iC3b and Bb) and C9 level (membrane attack complex) were measured in both plasma and urine of patients with minimal change nephrotic syndrome (MCNS), focal glomerular sclerosis, IgA nephropathy, membranous nephropathy, and diabetic nephropathy. For evaluation of the effect of metabolic acidosis on the intratubular complement activation, urinary CAP were measured before and after sodium bicarbonate administration in patients with renal insufficiency. The following results were obtained: (1) Patients with focal glomerular sclerosis and diabetic nephropathy showed the highest level of urinary CAP excretion rate (unit/creatinine), while MCNS revealed no increase. (2) Patients with membranous nephropathy showed a unique finding, i.e., isolated increase of membrane attack complex excretion. (3) There was no significant correlation between urine and plasma levels of CAP. (4) Except for MCNS patients, the urinary excretion rate of CAP significantly increased when the level of proteinuria exceeded the nephrotic range, and it was significantly correlated with the serum creatinine level. (5) Urinary CAP excretion rate significantly decreased 2 wk after sodium bicarbonate administration without affecting the level of proteinuria or plasma CAP. These results suggest that the degree of intratubular complement activation correlates with the level of proteinuria, type of glomerular disease, impairment of renal function, and metabolic acidosis.
Transition metals and polyol pathway in the development of diabetic neuropathy in rats.
BACKGROUND: The transition metal-catalyzed reaction is a major source of oxygen free radicals, which play an important role in vascular dysfunction leading to ischemia in diabetic tissues. The inhibition of polyol pathway hyperactivity has been reported to ameliorate neurovascular abnormalities in diabetic rats and has been proposed to improve the oxygen free radical scavenging capacity. The present study was conducted to compare the effect of a transition metal chelating agent, trientine (TRI), on diabetic neuropathy with that of an aldose reductase inhibitor, NZ-314 (NZ). METHODS: Diabetic rats were divided into three groups: (1). untreated, (2). TRI-treated, and (3). NZ-treated. TRI (20 mg/kg) or NZ (100 mg/kg) was administered by gavage or chow containing NZ, respectively, for 8 weeks. Motor nerve conduction velocity (MNCV), coefficient of variation of the R - R interval on electrocardiogram (CVr-r), sciatic nerve blood flow (SNBF), platelet aggregation activities, and serum concentrations of malondialdehyde were measured. RESULTS: Untreated diabetic rats showed delayed MNCV, decreased CV(R-R), and reduced SNBF compared to normal rats. TRI or NZ completely prevented these deficits. Platelet hyperaggregation activities in diabetic rats were prevented by NZ, but not by TRI. Increased concentrations of malondialdehyde in diabetic rats were partially but significantly ameliorated by either TRI or NZ. CONCLUSIONS: These observations suggest that increased free radical formation through the transition metal-catalyzed reaction plays an important role in the development of diabetic neuropathy and that the preventive effect of an aldose reductase inhibitor on diabetic neuropathy may also be mediated by decreasing oxygen free radicals.
Polyol pathway and protein kinase C activity of rat Schwannoma cells.
BACKGROUND: Polyol pathway hyperactivity-induced decreases in protein kinase C (PKC) activities have been proposed as a pathogenic mechanism of diabetic neuropathy. Increased PKC activities have recently been invoked in the pathogenesis of other diabetic complications, especially retinopathy, nephropathy, and macroangiopathy. However, it remains unclear whether PKC activities in neural cells such as Schwann cells are increased, decreased, or unchanged. This study investigated the effects of high glucose and increased polyol pathway activity on neural cell growth and PKC activities. METHODS: Rat Schwannoma cells were cultured in 5.5 or 20 mM glucose in the presence or absence of an aldose reductase inhibitor, epalrestat (1 microM) for 14 days. Proliferation activities, PKC activities, and the protein expression of PKC isoforms were measured. RESULTS: Proliferation and PKC activities under the 20 mM glucose condition were significantly decreased compared to those under the 5.5 mM glucose condition and were prevented by epalrestat. Among PKC isoforms, the protein expression of PKC-alpha under the 20 mM glucose condition was significantly reduced compared to that under the 5.5 mM glucose condition. Epalrestat significantly inhibited the decreased expression of PKC-alpha protein. There were no significant changes in the protein expression of PKC-beta. CONCLUSIONS: These results suggest that PKC, especially PKC-alpha activity, is decreased in Schwann cells exposed to high glucose and that this deficit is mediated through polyol pathway hyperactivity.
A copper chelating agent suppresses carbonyl stress in diabetic rat lenses.
To clarify whether transition metals are involved in carbonyl stress in diabetic tissues, we observed the effects of a metal chelating agent, trientine (TE) hydrochloride on the levels of methylglyoxal (MG), 3-deoxyglucosone (3-DG), advanced glycation end products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and polyol pathway metabolites along with semicarbazide-sensitive amine oxidase (SSAO) enzyme activity in lenses from streptozotocin-induced diabetic rats. Lens MG and 3-DG levels were significantly higher in diabetic rats than nondiabetic controls, and TE significantly restored the increase of these compounds. Lens argpyrimidine was also increased in diabetic rats as compared with controls and was significantly reduced by TE. Lens SSAO activity and 8-OHdG were also significantly elevated in diabetic rats, and TE suppressed both of them, whereas TE showed no effect on the polyol pathway metabolites. The results indicate that transition metals play a significant role in the formation of MG and 3-DG via oxidative stress and SSAO activity.
A muscle transposition procedure for abducens palsy, in which the halves of the vertical rectus muscle bellies are sutured onto the sclera.
PURPOSE: To review the results of a muscle transposition procedure in which the halves of the vertical rectus muscle bellies are sutured onto the sclera, without tenotomy of vertical recti as in Hummelsheim's procedure or surgical treatment of the lateral rectus (LR) as in Jensen's procedure. METHODS: Ten patients with abducens palsy received the procedure. We measured the ocular deviation and the field of single binocular vision, and observed the LR using magnetic resonance imaging (MRI). RESULTS: Preoperative or postoperative deviation was distributed from +27 to +58 prism diopters (PD) or orthophoria to +12 PD, respectively, in 7 patients with unilateral paresis, and +75 to +120 PD or +2 to +37 PD in 3 patients with bilateral paresis. The average correction was 42.4 PD per eye. Seven patients were able to regain the field of single binocular vision at least in the primary position. No postoperative complications were observed. MRI showed that the LR was atrophic and floppy, lacking muscle tension. CONCLUSIONS: Our procedure enabled the patients to obtain satisfactory postoperative results without treatment of the LR or tenotomy of the transposed muscles. This procedure can reduce operative damage to the eye more than Hummelsheim's or Jensen's procedure.
Regulation of the human taurine transporter by oxidative stress in retinal pigment epithelial cells stably transformed to overexpress aldose reductase.
In diabetes, overexpression of aldose reductase (AR) and consequent glucose-induced impairment of antioxidant defense systems may predispose to oxidative stress and the development of diabetic complications, but the mechanisms are poorly understood. Taurine (2-aminoethanesulfonic acid) functions as an antioxidant, osmolyte, and calcium modulator such that its intracellular depletion could promote cytotoxicity in diabetes. The relationships of oxidative stress and basal AR gene expression to Na+-taurine cotransporter (TT) gene expression, protein abundance, and TT activity were therefore explored in low AR-expressing human retinal pigment epithelial (RPE) 47 cells and RPE 47 cells stably transformed to overexpress AR (RPE 75). Changes in TT gene expression were determined using a 4.6-kb TT promoter-luciferase fusion gene. Compared with RPE 47 cells, in high AR-expressing RPE 75 cells, TT promoter activity was decreased by 46%, which was prevented by an AR inhibitor. TT promoter activity increased up to 900% by prooxidant exposure, which was associated with increased TT peptide abundance and taurine transport. However, induction of TT promoter activity by oxidative stress was attenuated in high AR-expressing cells and partially corrected by AR inhibitor. Finally, exposure of RPE 75 cells to high glucose increased oxidative stress, but down-regulated TT expression. These studies demonstrate for the first time that the TT is regulated by oxidative stress and that overexpression of AR and high glucose impair this response. Abnormal expression of AR may therefore impair antioxidant defense, which may determine tissue susceptibility to chronic diabetic complications.