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Biomedical subjects

N Komine

Publications and source records attributed to N Komine.

12 recordsLinked to original sources
PubMed2001

[Diabetic nephropathy; clinical stage and prediction].

Diabetic nephropathy(DN) is the leading cause of end-stage renal disease in Japan. Clinical course of DN is divided into five stages. Stage 1 is a pre-nephropathy stage. Stage 2 is the period with microalbuminuria. Stage 3A is the stage with persistent macroproteinuria and well preserved renal function. Strict glycemic control and antihypertensive treatment with ACE inhibitors are capable of inducing remission in stage 2 of DN and probably in stage 3A. GFR less than 60 ml/min and urinary protein excretion more than 1 g/day are regarded as stage 3B. Serum creatinine concentration increases in stage 4. Antihypertensive therapy and low protein diet are major options of therapy both in stage 3B and 4. Stage 5 is the period with renal replacement therapy. Survival rate of patients on HD due to DN still remains unsatisfactory. Only 30-50% of type 2 diabetic patients develop DN, suggesting that there are several factors other than hyperglycemia which induce DN. Prediabetic hypertension and parenteral hypertension are regarded as predictors of DN. Smoking, male gender, and advanced age might be risk factors of DN. Recently it was demonstrated that insertion/deletion(I/D) polymorphism of angiotensin converting enzyme gene is associated with DN. In addition polymorphisms of several genes seem to be associated with DN. Development of DNA tips will make it possible to determine a number of gene polymorphisms. Accumulations of the information on gene polymorphisms from many patients with or without DN are expected to contribute detection of patients at high risk of developing DN.

Aging↗
PubMed2000

External chiral ligand-induced enantioselective versions of the [2,3]-Wittig sigmatropic rearrangement.

The external chiral ligand-induced enantioselective [2,3]-Wittig rearrangements of crotyl benzyl ethers and crotyl propargylic ethers are described. The most notable is that treatment of (E)-crotyl propargylic ethers with a t-butyllithium/(S;S)-bis(oxazoline) complex provides a relatively high enantioselectivity (up to 89% ee), together with a high threo-diastereoselectivity. Furthermore, examples of the "asymmetric catalytic version" of the rearrangement of crotyl benzyl ethers are presented.

Journal Article↗
PubMed1999

Differences in heart rate variability between young and elderly normal men during graded head up tilt.

An autoregressive spectral analysis of heart rate variability (HRV) was used to analyze the differences in autonomic functions during graded head up tilt (HUT) between young and elderly men. After recording at the 0 degree position, the table was rotated to an upright position. The incline of the table was increased progressively to 15 degrees, 30 degrees and 60 degrees. The data obtained from seven young subjects (mean age of 20.0 years) and nine elderly subjects (mean age of 63.3 years) were analyzed. The high frequency components expressed by normalized units (HFnu) were used as the parasympathetic indicators, and HFnu decreased with tilt angle in both age groups. These results suggested that parasympathetic withdrawal have an important role in adaptation to an upright posture in both age groups. However, mean HF amplitude at the 0 degree position in elderly men was not significantly different from that of young men at 60 degrees tilt. A significant interaction effect (age group x tilt angle) was found for mean HF amplitude. The increase of the low frequency components expressed by normalized units (LFnu) and the LF-to-HF ratio in elderly subjects from 0 degree to 15 degrees seemed to be larger than that in young subjects. Sympathetic activities may be sensitive to lower levels of orthostatic stress in the elderly, and the elderly workers are easily affected by a change in workload. Therefore, keeping the workload lower and constant may be recommended to avoid excessive sympathetic activation among the elderly.

Adolescent↗
PubMed1998

Renal hemodynamics in rats with cadmium-induced nephropathy.

Glomerular filtration rate (GFR) is known to decline in patients with cadmium (Cd)-induced nephropathy. However renal hemodynamics in Cd-induced nephropathy remain unknown. We investigated renal hemodynamics in experimental Cd-induced nephropathy. Male Sprague-Dawley rats were given 0.18 mg/rat of cadmium chloride i.p. three times a week for 3 and 16 months. Age-matched control rats were given physiological saline. Mean arterial pressures after 3 and 16 months were identical among the groups. In comparison with age-matched control rats, significant decreases in GFR associated with a significantly lower filtration fraction (FF) were demonstrated in both groups of Cd-treated rats, but the changes were more prominent in the 16-month Cd-treated rats. Renal plasma flow was significantly decreased in the 3-month Cd-treated rats whereas it was preserved in the 16-month Cd-treated rats because of anemia. Urinary sodium excretions in both groups of Cd-treated rats were significantly greater than those in the respective control rats. On light microscopic examination, only mild degeneration of tubular cells and interstitial edema in limited areas of the proximal tubules were observed in the 3-month Cd-treated rats. In the 16-month Cd-treated rats multifocal tubular atrophy and interstitial fibrosis in the outer cortex were noted. Electron microscopic examinations revealed conspicuous degenerative changes in the proximal tubular epithelial cells, diffuse thickening of glomerular basement membranes, and foot process fusions in 16-month Cd-treated rats. These data suggested that the decline in GFR in the Cd-treated rats resulted mainly from the decline in FF, which might be functional rather than structural in origin and might be associated with proximal tubular dysfunctions.

Animals↗
PubMed1998

Protein C activation by recombinant thrombomodulin in plasma.

Recombinant glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM), which partially improved the amino acid sequence of human urinary thrombomodulin (UTM), was expressed in C127 cells. GAG-UTM accelerates protein C activation by thrombin and also thrombin inhibition by antithrombin III (ATIII) in the buffer system. Both accelerating activities of GAG-UTM are more potent than those of unmodified recombinant UTM (r-UTM) without a GAG chain. As ATIII in plasma also inhibits protein C activation by a thrombin-thrombomodulin complex, we studied whether GAG-UTM accelerates protein C activation in plasma. GAG-UTM suppressed the generation of thrombin in activating plasma protein C stronger than r-UTM. By Western blot analysis using anti-protein C antibody, activated protein C was generated by GAG-UTM more than by r-UTM. From these results, the acceleration of activated protein C formation by GAG-UTM was confirmed in plasma too.

Blotting, Western↗
PubMed1998

Increased anticoagulant activity of recombinant thrombomodulin modified with glycosaminoglycan.

Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface, effective as an anticoagulant by changing procoagulant thrombin to an anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent anticoagulant activity than that without GAG, we expressed recombinant GAG-modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an additional GAG chain on anticoagulant activity was investigated in comparison with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of fibrinogen by thrombin or prothrombinase activity was more potently depressed by GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin complex was accelerated by GAG modification. The acceleration of antithrombin III-dependent anticoagulant activity was shown only by GAG-UTM. Parameters like thrombin time, prothrombin time and activated partial thromboplastin time in human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM significantly reduced the decrease in fibrinogen and platelet number induced by endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time induced by endotoxin, while r-UTM accelerated it. These results suggest that the addition of a GAG chain may increase availability as an anticoagulant.

Angiotensin III↗
PubMed1994

Acute and chronic effects of thromboxane A2 inhibition on the renal hemodynamics in streptozotocin-induced diabetic rats.

We examined acute and chronic effects of thromboxane (TX) A2 inhibition on the renal hemodynamics at early and late stage of untreated streptozotocin (STZ)-induced diabetic rats. Two weeks and 28 weeks after the induction of diabetes, renal blood flow (RBF) under anesthesia was measured with an electromagnetic flowmeter before and after TXA2 inhibition. In two-week-old diabetic rats, a specific TXA2 synthetase inhibitor, OKY-046, or a specific TXA2 receptor antagonist, Sulotroban, increased renal vascular resistance (RVR) and ameliorated the hyperperfusion. The renal vasoconstrictive effect of OKY-046 was blunted by an angiotensin converting enzyme (ACE) inhibitor, MK422, or an angiotensin II receptor antagonist, Saralasin. On the contrary, OKY-046 ameliorated the renal hypoperfusion by decreasing RVR in 28-week-old diabetic rats. Chronic oral administration of OKY-046 ameliorated not only the renal hyperperfusion but increased urinary albumin excretion (UAE) at two weeks, but also the renal hypoperfusion, filtration fraction and UAE at 24 weeks. It is suggested that TXA2 might, at least in part, play important roles in the hyperperfusion by modulating activity of the renin-angiotensin system at an early stage of untreated diabetic rats and in the hypoperfusion at the late stage of untreated diabetic rats, and that TXA2 is also involved in the increase of UAE. These results support roles for TXA2 in the progression of renal injury in STZ-induced diabetic rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[The effects of acute administration of cadmium chloride on renal hemodynamics in rats].

The decreases of glomerular filtration rate (GFR) and renal blood flow (RBF) after acute administration of cadmium have been reported. The recent studies about renal failure induced by heavy metals revealed that the decrease of glomerular ultrafiltration coefficient is an important contributing factor in the onset of acute renal failure and that the changes of renal hemodynamics are less prominent factors. To clarify whether the changes of renal hemodynamics contribute to the decrease of GFR caused by cadmium, we evaluated the changes of renal hemodynamics and inulin clearance after acute intravenous infusion of cadmium chloride in rats. Cadmium chloride was continuously infused at the rate of 3.0 mumol/kg/min into SD rats. Mean arterial pressure was significantly increased immediately after the infusion of cadmium and unchanged during the experiment. 20 minutes after the infusion of cadmium, inulin clearance was decreased by 70% of the control value but RBF and renal vascular resistance (RVR) were unchanged. Filtration fraction was significantly decreased. 30 minutes after the infusion of cadmium, inulin clearance was further decreased by 51% of the control value. At the period, significant decrease of RBF (72% of control value) and increase of RVR (156% of control value) were observed. Urinary excretion of sodium and the ratio of urinary sodium to urinary inulin excretion were unchanged until 20 minute and were significantly decreased 30 minutes after the infusion of cadmium. Urinary volume was not changed throughout the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1991

[Clinical significance of urinary FDP-E measured by latex photometric immunoassay (LPIA) in the renal disease].

It is well known that urinary FDP is one of the parameters of intrarenal coagulation in renal disease. The measurement of urinary FDP, however, is not satisfactory enough, since it is not a quantitative and sensitive method. Latex photometric immunoassay has recently been developed as a quantitative and more sensitive method. Since fibrinogen reacts with FDP-E less than FDP, the measurement of urinary FDP-E is much better than that of urinary FDP in order to determine the presence of intrarenal coagulation and fibrinolysis of patients with renal diseases. The aim of this study is to clarify the clinical significance of urinary FDP-E measured by LPIA in the renal disease. The results were as follows: (1) Urinary FDP-E correlate with urinary protein, FDP, FDP-D, fibrinopeptide A (FPA), but not serum FDP-E. (2) The diseases which showed higher amounts of urinary FDP-E were diabetic nephropathy, amyloidosis and chronic glomerulonephritis. On the other hand, the diseases which showed smaller amounts of urinary FDP-E were minimal change, toxemia of pregnancy and lupus nephritis. All patients with higher amounts of urinary FDP-E showed marked renal dysfunction. But all the patients with the marked renal dysfunction did not always show higher amounts of urinary FDP-E. The urinary FDP-E showed a positive correlation to 1/serum creatinine. These results suggested that the measurement of urinary FDP-E is a useful method in determining the presence and degree of intrarenal coagulation and fibrinolysis in renal diseases.

Adult↗
PubMedDate not supplied

Clinical significance of urinary enzymes in diabetic nephropathy.

Urinary enzyme activities (N-acetyl-beta-D-glucosaminidase [NAG], alkaline phosphatase [ALP], leucine aminopeptidase [LAP], gamma-glutamyl transpeptidase [gamma-GTP]) were investigated to determine their clinical significance in diabetic nephropathy. There were correlations among ALP, LAP, and gamma-GTP, though no correlation existed between NAG and the other three enzymes. Activities of NAG isozymes (both A and B) were higher than in normal controls. It has been reported that NAG isozyme A might be associated with glomerular diseases, and isozyme B might be associated with proximal tubular damage. The results of our study suggest that NAG reflects lysosomal dysfunction of both glomerular and proximal tubular epithelial cells, which may be caused by poor glycemic control, and that ALP, LAP, and gamma-GTP reflect brush border damage of proximal tubules, which may be caused by diabetic nephropathy.

Acetylglucosaminidase↗
PubMedDate not supplied

The characteristics of renal hemodynamics in diabetic spontaneously hypertensive rats in comparison with diabetic Wistar-Kyoto rats.

Diabetic Sprague-Dawley (SD) rats are known to exhibit renal hyperfiltration and hyperperfusion accompanied by renal hypertrophy. We examined whether such characteristics of renal hemodynamics in diabetic SD rats are also observed in diabetic spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. SHR and WKY rats were divided into four groups: D-S, diabetic SHR; N-S, nondiabetic SHR; D-W, diabetic WKY rats; and N-W, nondiabetic WKY rats. Streptozotocin (STZ), 90 mg, was intraperitoneally injected to induce diabetes. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by a clearance method with paraaminohypurate and insulin, respectively, 7-12 days after diabetes induction. In D-S and D-W, there was no increase in the kidney weight and RBF, in spite of significant increases in GFR and fasting blood sugar levels. These results indicate that, in both WKY and SHR, diabetes does not always produce renal hypertrophy and does not result in an increase in RBF.

Animals↗