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Biomedical subjects

K Tabei

Publications and source records attributed to K Tabei.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cystatin C measurement and its practical use in patients with various renal diseases.

OBJECTIVE: To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the cystatin C levels in the serum and urine of 33 healthy volunteers as well as in the serum and urine of 35 patients with various renal diseases and compared them with those of creatinine. In addition, we evaluated this substance as an indicator of removal rate of low molecular weight protein with high flux membranes in 6 hemodialysis (HD) patients. METHODS: Serum and urinary cystatin C levels were measured by using an enzyme-linked immunosorbent assay (ELISA) method, 24-hour creatinine clearance was used as an indicator of GFR. RESULTS: Reference intervals with 95% ranges are 0.47-1.03 mg/l in the serum from healthy volunteers. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.936, p < 0.001) in the patients with various renal diseases. Serum cystatin C and creatinine inversely and logarithmically correlated to creatinine clearance as shown in the following equations: log cystatin C = -0.564 x log creatinine clearance + 1.216 (r = -0.850), log creatinine = -0.678 x log creatinine clearance + 1.449 (r = -0.904). In these equations l/day is the unit used for creatinine clearance, mg/l is the unit used for serum cystatin C. The range for cystatin C is 0.67-6.15 mg/l, 0.66-7.23 mg/dl for creatinine and 8.9-186.3 l/day (6.2-129.4 ml/min) for creatinine clearance. Serum cystatin C levels started to increase over normal range when creatinine clearance fell below 135.9 l/day (94.4 ml/min), while serum creatinine remained within normal ranges. The daily urinary excretion of cystatin C was increased significantly in the group in which creatinine clearance was below 30 l/day (20.8 ml/min) compared to that in which creatinine clearance was higher than in 70 l/day (48.6 ml/min). Fractional clearance of cystatin C increased proportionally and markedly to the decrease of creatinine clearance. In a regular HD condition with high flux membrane, the cystatin C removal rate was 38.7 +/- 1.7%. CONCLUSIONS: These data suggest that combined measurement of cystatin C in the serum and urine is useful to estimate GFR, especially to detect the mild reduction of GFR. Cystatin C measurement can also be used as an indicator of removal rate of low molecular weight protein with different types of high flux membranes in hemodialysis.

Adult↗
PubMed1996

Inhibition of human cytomegalovirus UL80 protease by specific intramolecular disulfide bond formation.

A symmetrically substituted disulfide compound, CL13933, was identified as a potent inhibitor of human cytomegalovirus UL80 protease. Two types of inhibited protease were observed, depending on inhibitor concentration. At high concentrations, CL13933 formed a covalent adduct with the protease on Cys residues. At lower concentrations, this compound induced specific intramolecular disulfide formation between Cys84 and Cys87, and between Cys138 and Cys161. In contrast, Cys202 did not form disulfide bonds. Inhibition was reversed upon reduction of the protease. Each of the five cysteines of the UL80 protease was individually mutated to Ala. Each of the mutant proteases retained enzymatic activity, but mutants C138A and C161A were resistant to inhibition by CL13933, suggesting that disulfide bond formation between Cys138 and Cys161 is responsible for inhibition. This disulfide is apparently not induced by air oxidation. Examination of the CL13933 loading patterns of wild type and the five mutant proteases by mass spectrometry revealed that residues Cys87, Cys138, and Cys161 react with CL13933, and that the disulfide pair partner of each (Cys84, Cys161, and Cys138, respectively) is able to displace the compound via thiol-disulfide exchange. The possible significance of these reactive thiols in the protease is discussed.

Amino Acid Sequence↗
PubMed1996

Flavins inhibit human cytomegalovirus UL80 protease via disulfide bond formation.

Among the most potent inhibitors of human cytomegalovirus protease identified by random screening of a chemical library was 1,4-dihydro-7,8-dimethyl 6H-pyrimido[1,2-b]-1,2,4,5-tetrazin-6-one (1) (PTH2). The oxidized form (2), PT, which is present in solutions of PTH2, was shown to be the actual inhibitory species which irreversibly inactivates the protease; recycling of PTH2 by dissolved oxygen results in complete inhibition of the protease at substoichiometric amounts of compound. No evidence for a covalent adduct between the protease and the inhibitor was obtained, and protease activity was restored by incubation of the inactivated enzyme with the reducing agent bismercaptoethyl sulfone, suggesting that disulfide bond formation was responsible for the observed inhibition. The five cysteines of the protease are normally in the reduced state; analysis of tryptic peptides from inhibited protease indicated that disulfide bonds Cys84-Cys87 and Cys138-Cys161 were formed. Using site-directed mutagenesis, the disulfide pair induced between Cys138 and Cys161 disulfide is dependent upon interaction of PT with the protease and does not form spontaneously, unlike that of the Cys84-Cys87 pair which can form in the absence of inhibitor. The inhibitor's redox chemistry is analogous to that of flavin, and, in fact, flavin inhibits the protease by the same mechanism, causing formation of a disulfide bond between Cys138 and Cys161. That the cysteines are dispensable, but can regulate protease activity by formation of a unique disulfide pair, suggests a plausible mechanism for control of proteolysis during the viral life cycle.

Base Sequence↗
PubMed1996

Additional mechanisms of nafamostat mesilate-associated hyperkalaemia.

OBJECTIVE: Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potassium excretion, of the drug suppression of aldosterone secretion, and a direct inhibitory action on the apical Na+ conductance in collecting ducts. We have seen two cases of nafamostat mesilate associated-hyperkalaemia, which indicated that extrarenal potassium imbalance might play a role in inducing hyperkalaemia. METHODS: To examine the effect of nafamostat mesilate on potassium transport in erythrocytes in vitro, 86RbCl uptake was measured in red blood cells from eight healthy volunteers. RESULTS: Nafamostat mesilate and a metabolite, 6-amidino-2-naphthol, at concentrations of 10(-4) and 10(-3) M, respectively, significantly, suppressed potassium influx whilst another metabolite, p-guanidino-benzoic acid, had no effect. The inhibitory action of nafamostat mesilate was not affected by various inhibitors. CONCLUSION: Nafamostat mesilate and its metabolite, 6-amidino-2-naphthol, suppressed potassium influx in erythrocytes by inhibition of a Na-K ATPase dependent pathway, which was not inhibited by amiloride, barium, nor by frusemide (furosemide).

Adult↗
PubMed1996

A study on regulating factors of plasma refilling during hemodialysis.

Hypotension is frequently encountered during hemodialysis (HD). One of the main factors of the HD-induced hypotension is acute reduction of circulating plasma volume by water removal, which is induced by the poor plasma refilling from the extravascular space into vessels. The determinants of plasma refilling, however, have not been clearly identified. Recently, we devised a mathematical model of water transport in HD patients, which can estimate the plasma-refilling coefficient (Kr) during HD. In the present study, we evaluated the factors determining plasma refilling by using this model. In 13 patients undergoing regular HD, the changes of Kr during HD were calculated from the model. Levels of ANP, cGMP, cAMP, endothelin, angiotensin II and vasopressin were measured before and after HD. Kr fell from 750.4 +/- 558.0 to 112.8 +/- 81.9 ml/mm Hg/h during HD. The rate of water removal during HD showed no significant correlation with the changes of Kr. Among the hormones and nucleotides measured here, plasma ANP level and cGMP were significantly correlated with Kr (r = 0.78, p < 001 and r = 0.62, p < 0.01, respectively). Our findings suggest that severe reduction in the level of serum ANP during HD, which is induced by water removal, plays some role in HD-induced hypotension through the attenuation of plasma refilling in HD patients.

Adult↗
PubMed1996

An index of plasma refilling in hemodialysis patients.

During hemodialysis therapy, a large amount of water is removed from the patient's blood in a short time; however, blood pressure remains stable in most patients. As water is removed, the circulating serum proteins become more concentrated, resulting in a marked increase in the driving force which pulls water from the extravascular space into the blood vessels, by a process called plasma refilling. However, since a method for studying plasma refilling has not previously been proposed, it is not known what determines the plasma refilling capacity of hemodialysis patients. To evaluate the plasma refilling capacity of patients, we propose here a method for calculating an index of plasma refilling capacity, which we have called the plasma-refilling coefficient (Kr). In 14 patients receiving maintenance hemodialysis therapy, total serum protein was measured before hemodialysis, and hematocrits were measured hourly during hemodialysis. From the changes in the hematocrits, we estimated the changes in the circulating plasma volume and in the intracapillary oncotic pressure at each time point. The water removal rate was also measured hourly. From these values, we calculated Kr. An averaged volume of 2,692 +/- 219 ml of water was removed from each patient resulting in a decrease in the estimated circulating blood volume, while the hematocrit and the estimated intracapillary oncotic pressure increased gradually. Kr calculated after 1 h of hemodialysis varied widely between patients, 140.3-1,744.2 ml/mm Hg/h, and decreased gradually as water removal continued. The average Kr of 14 patients was 698.9 +/- 15.2 ml/mm Hg/h at the beginning of water removal, and it decreased to 405.3 +/- 75.4, 203.9 +/- 39.5, 130.2 +/- 20.5 and 93.9 +/- 14.3 each hour thereafter. The index of plasma refilling proposed in this paper is useful for examining capillary water permeability and the degree of plasma refilling in hemodialysis patients.

Adult↗
PubMed1995

Role of [Ca2+]i in lethal oxidative injury in rat cultured inner medullary collecting duct cells.

Reactive oxygen metabolites have been implicated in the pathogenesis of toxic, ischaemic and immunologically mediated renal injury. An increase in the cytosolic free Ca2+ concentration ([Ca2+]i) has been proposed as a mechanism of oxidative stress-induced cell injury. We used a fluorescence spectrometer and a fluorescence probe to measure the [Ca2+]i and viability of rat primary cultured inner medullary collecting duct (IMCD) cells during oxidative stress induced by 5 mM tert-butyl hydroperoxide (TBHP). Initially, this oxidative stress evoked a small increase in [Ca2+]i which was followed by a slower sustained increase from the resting level of 170.8 +/- 38.8 nM to 1490.5 +/- 301.7 nM after 60 min, and this preceded the loss of plasma membrane integrity, measured by the propidium iodide fluorescence method. The elimination of extracellular Ca2+ from the culture medium prevented the TBHP-induced [Ca2+]i increase and improved cell viability. Restoration of extracellular Ca2+ resulted in an immediate and large increase in [Ca2+]i and extensive cell death. Verapamil, a Ca2+ channel blocker, inhibited the [Ca2+]i increase and afforded significant protection against cellular injury following exposure to TBHP-induced oxidative stress. Extracellular acidosis also prevented the increase in [Ca2+]i and cell death caused by this oxidative stress. These results are consistent with the hypothesis that oxidative stress-induced IMCD cellular injury may be the result of increased [Ca2+]i caused, in part, by activation of voltage-dependent Ca2+ channels.

Animals↗
PubMed1995

Potassium secretion is inhibited by metabolic acidosis in rabbit cortical collecting ducts in vitro.

The role of metabolic acidosis in the regulation of transepithelial potassium transport was examined in rabbit cortical collecting ducts (CCD) using in vitro isolated tubular microperfusion and conventional microelectrode techniques. Basolateral metabolic acidosis, created by reduction of bicarbonate concentration from 25 to 5 meq/l, pH 7.40 to 6.80, depolarized the transepithelial voltage significantly (-6.5 +/- 1.0 to -2.7 +/- 1.3 mV). Basolateral acidosis also suppressed net potassium secretion (-14.3 +/- 2.1 to -9.0 +/- 1.7 pmol.min-1.mm-1). Electrophysiological study in CCD cells demonstrated that basolateral metabolic acidosis depolarized transepithelial voltage and apical and basolateral membrane voltage with an increase of transepithelial and fractional apical resistance. Basolateral acidosis did not affect the 22Na efflux nor 86Rb efflux. The inhibitory action of basolateral acidosis on net potassium secretion remained in the presence of luminal barium and in the absence of bicarbonate. Ouabain could not abolish the effect of basolateral acidosis on transepithelial voltage completely. These data lead us to conclude that basolateral acidosis affects multiple transport pathways, and it inhibits mainly apical barium-sensitive potassium transport. Additionally, it inhibits apical sodium conductance, barium-insensitive potassium transport, and stimulates a ouabain-insensitive electrogenic transport pathway to some degree.

Acidosis↗
PubMed1994

Interleukin-1 inhibits sodium and water transport in rabbit cortical collecting duct.

Interleukin-1 (IL-1) induces natriuresis and diuresis. In the present study, the effect of basolateral IL-1 on sodium and water transport was examined in the cortical collecting duct (CCD) perfused in vitro. IL-1, 10 pg/ml and 10 ng/ml, inhibited lumen-to-bath sodium flux (JNa, peq.min-1.mm tubule-1), depolarizing transepithelial voltage (Vt) in a time- and dose-dependent manner. The inhibitory effect of 10 ng/ml but not 10 pg/ml IL-1 on Vt and JNa was mitigated by 5 microM indomethacin (IND) in bath. Also, 10 ng/ml IL-1, which did not affect the basal hydraulic conductivity (Lp, x10(-7) cm.atm-1.s-1) by itself, inhibited the hydrosmotic effect of 20 pM basolateral arginine vasopressin, and 5 microM IND abolished this inhibitory effect of 10 ng/ml IL-1. The present study demonstrated direct inhibitory effect of basolateral IL-1 on sodium and water reabsorption in the rabbit CCD. The effect of IL-1 is suggested to be mediated, in part, by a cyclooxygenase metabolite(s).

Animals↗
PubMed1994

Axial heterogeneity of potassium transport across hamster thick ascending limb of Henle's loop.

Functional significance of morphological heterogeneities along the thick ascending limb of Henle's loop of hamsters was explored by the in vitro microperfusion technique with special reference to K+ transport. The transmission electron microscopic study confirmed that there are two types of cells, with smooth surface (S-cell) and rough surface (R-cell), respectively, and that the former is abundant in the medullary thick ascending limb (MTAL), whereas the latter is in the cortical portion (CTAL). The electrophysiological study revealed that in both segments there are two cell populations, one having high basolateral and low apical membrane K+ conductances (HBC) and the other having low basolateral and high apical K+ conductances (LBC). Random cell puncture revealed that the ratios of HBC/LBC were 24/7 (77%/23%) in the MTAL and 7/22 (24%/76%) in the CTAL, suggesting that HBC corresponds to S-cell, whereas LBC corresponds to R-cell. Net K+ transport was determined in two segments by measuring K+ concentration in the collected and perfused fluid by ultramicroflame photometry. In all six tubules of MTAL, net K+ flux had a direction to reabsorption with a mean of 4.87 +/- 0.46 pmol.min-1.mm-1. In marked contrast, in all six tubules of CTAL, we observed K+ secretion with a mean of -3.81 +/- 0.49 pmol.min-1.mm-1. The transmural voltage was positive in both segments and was significantly higher in the CTAL (7.8 +/- 0.5 mV) than in the MTAL (2.5 +/- 0.2 mV). From these observations, we conclude that the S-cell corresponding to the HBC cell reabsorbs K+, whereas the R-cell corresponding to the LBC cell secrets K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Enhanced volume-sensitive K flux in patients on chronic hemodialysis.

Swelling-activated K flux was investigated in erythrocytes from patients on regular hemodialysis. K influx, measured by 86Rb uptake, was increased in hemodialysis patients from 25.5 +/- 0.6 to 47.3 +/- 3.4 nmol/10(9) cells/h (n = 4, p < 0.01), when the medium osmolarity of Hepes buffer was decreased by 100 mosm/kg H2O. In normal subjects, K influx was also stimulated from 28.1 +/- 1.2 to 37.8 +/- 2.1 nmol/10(9) cells/h (n = 4, p < 0.01). The swelling-activated increment of K influx was comparatively higher in hemodialysis patients (85.5 vs. 34.5% in controls). Reduction of the medium osmolarity by 100 mosm/kg H2O also caused a larger increase of K efflux in hemodialysis patients than in control subjects (171.1 vs. 118.1%). K efflux was increased even in the presence of 10(-4) M ouabain (from 284 +/- 25 to 879 +/- 122 nmol/10(9) cells/h), although the increment of K efflux was completely abolished when Cl was replaced by gluconate (555 +/- 47 nmol/10(9) cells/h with Cl and 467 +/- 44 nmol/10(9) cells/h without Cl). These data suggest that in hemodialysis patients, swelling-activated K transport is enhanced via activation of the Cl-dependent ouabain-insensitive K transport pathway.

Adult↗
PubMed1993

Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria in chronic glomerular disease.

The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor, captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60 years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed by renal biopsy. Eight of the 14 patients had received antihypertensive drugs such as calcium channel blockers, diuretics or beta-blockers. Captopril was added to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients. Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within three months after the start of administration. In 4 patients (28.6%), the extent of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure, creatinine clearance and serum creatinine were not changed significantly. There was a positive linear correlation between the extent of reduction of proteinuria and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that captopril reduces proteinuria in some patients with IgA nephritis whose plasma renin activity responds to the drug.

Adult↗
PubMed1993

[Hemofiltration for the treatment of patients with congestive heart failure].

Hemofiltration is usually performed to patients with renal failure but is also an effective method for treating patients with congestive heart failure due to various causes such as hypotension, low cardiac output, oliguria and anasarca. By continuing 24hr a day at low blood flow rate, CAVH (Continuous Arteriovenous Hemofiltration) or CVVH (Continuous Venousvenous Hemofiltration) can remove the body fluid up to 500 ml/hr without much affecting systemic circulation. Successive management of body fluid even results in the recover of renal insufficiency due to decreased renal blood flow or drug overload. To perform hemofiltration safely, it is important to monitor the systemic circulation. Usually we monitor the diameter of IVC (Inferior vena cava) with ultrasonography thought the procedure the to detect changes in blood volume simultaneously.

Anticoagulants↗