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A Fukuzaki

Publications and source records attributed to A Fukuzaki.

At least 19 recordsLinked to original sources
PubMed1999

Dynamin and rab5 regulate GRK2-dependent internalization of dopamine D2 receptors.

Dopamine D2 receptors (D2Rs; short form, which is one of the alternative splicing variants) expressed in COS-7 cells are internalized in an agonist-dependent manner only when G protein-coupled receptor kinase 2 (GRK2) is coexpressed [Ito, K., Haga, T., Lameh, J. & Sadée, W., (1999) Eur. J. Biochem. 260, 112-119]. We have examined the effects of coexpression of dynamin, a small molecular mass GTP-binding protein, rab5A, and their mutants on the internalization of D2Rs in the presence of both dopamine (10 or 100 microM) and GRK2. The rate and extent of D2R internalization was increased or decreased by coexpression of dynamin I or a dominant-negative form of dynamin I (dynamin I K44E), respectively. The effects of coexpressing these two dynamins were more prominent at 10 microM dopamine than at 100 microM. In the presence of 10 microM dopamine, internalization of D2R was completely suppressed when dynamin I K44E was coexpressed, and the half-life (t 1/2) of D2R internalization decreased relative to cells not expressing dynamin from 82 to 29 min when dynamin I was coexpressed. Internalization of D2Rs was facilitated or suppressed by coexpression of a constitutively active form of rab5A (rab5A Q79L) or a dominant-negative form of rab5A (rab5A S34N), respectively. The t 1/2 of D2R internalization at 10 microM dopamine decreased from 82 to 16 min in cells coexpressing rab5A Q79L. The effect of coexpression of rab5A S34N was more apparent at 100 microM dopamine than at 10 microM; the t 1/2 of D2R internalization at 100 microM dopamine increased from 20 to 56 min and the proportion of internalized D2Rs after 120 min decreased from 53 to 28%. These results indicate that the internalization of D2Rs is dependent on the action of dynamin as well as GRK2, and is regulated by the action of rab5A.

Animals↗
PubMed1999

Role of protein kinase C in cisplatin nephrotoxicity.

BACKGROUND: Cisplatin is widely used in cancer treatment. The major disadvantage of this antitumor agent is its nephrotoxicity. The mechanism of cisplatin-induced nephrotoxicity has not been clarified. Recent evidence suggests protein kinase C (PKC)-related signal transduction pathways may modulate cisplatin-induced cytotoxicity. METHODS: The effect of cisplatin administration on PKC expression in the kidney and the effect of a PKC inhibitor on cisplatin-induced renal impairment were investigated in rats. RESULTS: A single intraperitoneal injection of 8 mg/kg cisplatin induced remarkable damage in the proximal tubules located in the outer medulla, which was associated with impaired renal function, within 48 h. An immunoblotting study revealed marked expression of alpha-PKC in membrane fractions of medullary tubules prepared from cisplatin-treated rats. In addition, pretreatment with the PKC inhibitor (H-7) protected kidneys from cisplatin-induced damage. CONCLUSIONS: These findings suggest that the nephrotoxic effects of cisplatin may, in part, be related to PKC activation in the renal tubules.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

[Laparoscopic investigation of 74 cases of nonpalpable testis].

BACKGROUND: The objective of this study is to evaluate the results and advantages of laparoscopic investigation of nonpalpable testis. METHOD: Since March 1986 to May 1996, we performed laparoscopy to investigate 88 nonpalpable testes of 74 cases under general anesthesia. On condition that testis was found intraabdominally, orchiectomy or orchiopexy was performed subsequently. With a finding of vas deferens and/or spermatic vessels entering into internal ring, inguinal canal was explored surgically. If both vas deferens and spermatic vessels were absent or blind-ending intraabdominally, no further examination was performed with a diagnosis of vanishing testis. RESULTS: Location of testes found in this study were as follows. Twenty three (26.1%) testes were found intraabdominally, 36 (40.9%) were intracanalicularly, 13 (14.8%) were distal to external inguinal ring, and 16 (18.2%) were vanishing testes. To those 39 (44.3%) intraabdominal and vanishing cases did not need inguinal exploration. CONCLUSION: In conclusion, a laparoscopic examination for nonpalpable testis is the most effective and less invasive procedure to make sure or preclude the location of the gonad. And in 18% of those who were enrolled in this study, no further surgical interventions were needed. An accurate locating of nonpalpable testis permits site-specific planning of surgical management.

Adolescent↗
PubMed1997

Unicalyceal kidney associated with ureteral anomalies.

A unicalyceal kidney is a very rare anomaly of the urinary system. We report 4 cases of unicalyceal kidneys in infants. All cases were associated with ureteral anomalies: megaureter on the involved side, and/or ectopic ureter with vesicoureteral reflux or renal agenesis on the contralateral side. In order to preserve renal function we recommend surgical treatment for patients with unicalyceal kidney when they have ureteral anomalies.

Abnormalities, Multiple↗
PubMed1996

Characterization of G proteins in obstructed kidneys.

BACKGROUND: Urinary tract obstruction has a marked effect on renal function. Activation of phospholipases which results in incremental production of vasoactive eicosanoids may contribute to the hemodynamic changes characteristic of an obstructed kidney. G proteins play an important role in transmembrane signal transduction, which control phospholipase activities and eicosanoid production. The present study was designed to determine the presence of G proteins in obstructed kidneys in rats, and to characterize the differences between unilateral ureteral obstruction (UUO) and bilateral ureteral obstruction (BUO). METHODS: Several G-protein alpha subunits (G alpha s, G alpha i1,2, and G alpha i3) and the beta subunit (G beta) were determined by immunoblotting and immunocytochemical techniques using specific antibodies against these G proteins. RESULTS: Immunoblots demonstrated a decreased G alpha i3 content in the outer medullary tubules and a significantly lower G beta level in the glomeruli of UUO. In BUO, there was an increased level of G beta in the cortical tubules, and the G alpha s level was markedly reduced in the inner medullary tubules. Immunocytochemical studies revealed that these G proteins were predominantly localized in the brush border side of the cortical tubules. However, we could not demonstrate staining differences between UUO and BUO. CONCLUSIONS: These results indicate that a modulation of G-protein-coupled transmembrane signal transduction may contribute to the renal functional changes in an obstructed kidney. A different level of expression of G-protein subunits between UUO and BUO may be a factor in the differences of hemodynamics and renal tubular damage between UUO and BUO.

Animals↗
PubMed1996

Characterization of protein kinase C expression in human kidney.

Protein kinase C (PKC), the calcium and phospholipid-dependent kinase, is a key enzyme for regulation of growth and differentiation of various cells and tissues. Abnormalities of PKC modulation may cause diseases such as neoplasia. The present study was designed to demonstrate localization of PKC in normal human nephron segments. Surgically extirpated specimens for renal tumor were used. PKC was determined by immunoblotting and immunohistochemical methods using specific antibody against PKC that recognizes alpha and beta subtypes of this enzyme. Immunoblotting study demonstrated PKC in the cytosolic fractions of homogenized cortical tubules and medullary tubules prepared from morphologically normal part of the kidney. PKC was faintly detected in glomerular supernatants. Immunohistochemical study revealed that PKC was present throughout the nephron and especially concentrated in the cytoplasm of the proximal tubules and the medullary collecting ducts. The results indicate that PKC appears to play a role in regulation of normal nephron function in human kidney.

Adult↗
PubMed1996

Determining the origin of hematuria by immunocytochemical staining of erythrocytes in urine for Tamm-Horsfall protein.

PURPOSE: We analyzed the feasibility of immunocytochemical staining of urinary erythrocytes for Tamm-Horsfall protein to differentiate renal from nonrenal hematuria. MATERIALS AND METHODS: Urine samples collected from 74 patients with hematuria were evaluated. Erythrocytes in urine were inspected morphologically and the same samples were immunocytochemically stained with antibody against human Tamm-Horsfall protein. RESULTS: Erythrocytes in urine were clearly stained for Tamm-Horsfall protein in renal hematuria. Tamm-Horsfall protein immunocytochemistry was more consistent with clinical diagnosis than morphology. CONCLUSIONS: Immunocytochemical staining of urine erythrocytes for Tamm-Horsfall protein appears to be a reliable tool to differentiate renal from nonrenal hematuria.

Diabetic Nephropathies↗
PubMed1995

Enhanced glomerular phospholipase activity in the obstructed kidney.

Previous study demonstrated that an increment of glomerular eicosanoid production may contribute to the haemodynamic changes in the obstructed kidney. To elucidate the mechanisms responsible for enhanced glomerular eicosanoid production, the present study was designed to investigate activities of related enzymes by isolated glomeruli from rat kidney with unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction (BUO) for 24 hours. The activity of phospholipase A2 (PLA2) was determined by monitoring 14C] arachidonate release using 14C] phosphatidylcholine (PC) or 14C] phosphatidylethanolamine (PE) as a substrate. Phospholipase C (PLC) activity was assayed by measuring the release of [3H] inositol triphosphate [3H] IP3 from [3H] phosphatidylinositol 4,5 biphosphate ([3H] IP2). The activity of PE-specific PLA2 was increased in glomeruli from the kidney with BUO and the contralateral kidney of unilateral ureteral obstruction (CLK). PLC activity was significantly greater in the cytosolic fraction of glomeruli from kidneys with UUO, BUO and CLK compared to sham-operated control. The activity of PC-specific PLA2 was not significantly increased in any group. These results indicate that the increased synthesis of eicosanoids by glomeruli from obstructed kidney may be mediated by enhanced activities of PE-specific PLA2 and PLC. The increased activities of these phospholipases by glomeruli from CLK may contribute to a compensatory response.

Animals↗
PubMed1995

[Obstructive and reflux nephropathy].

Urinary tract obstruction and vesicoureteral reflux have marked effects on renal function. Renal interstitial fibrosis and glomerular hypertrophy with subsequent focal segmental glomerulosclerosis like changes are a common consequence of chronic obstruction and vesicoureteral reflux. Evidence suggests that vasoactive compounds and cytokines such as angiotensin II, nitric oxide, eicosanoids, TNF, TGF, EGF, PDGF, bFGF have a role in the hemodynamic and structural abnormalities that occur following obstruction of the urinary tract or vesicoureteral reflux. Use of modulators for these compounds appears to be beneficial for treatment of obstructive or reflux nephropathy in near future.

Chronic Disease↗
PubMed1994

Localization of several G-protein subunits in human kidney.

Localization of guanine nucleotide binding protein (G-protein) alpha chains in human kidney was examined using immunoblotting and immunocytochemical techniques. Immunoblot studies revealed G alpha s, G alpha i1,2 and G alpha i3 proteins in membrane fractions of glomeruli, cortical tubules and medullary tubules. Immunocytochemical studies confirmed the presence of these G-proteins in several parts of human nephron. The results demonstrate the presence of a large amount of G-protein alpha subunits in human nephron segments. We speculate that G-protein in human kidney may play an important physiological role well-defined in other mammalia.

Cell Membrane↗
PubMed1993

Role of glomerular eicosanoid production in the obstructed kidney.

The regional production of prostaglandin E2 and thromboxane B2 was investigated in the kidney with unilateral or bilateral ureteral obstruction for 24 hours in rats. The production of these eicosanoids was highest in the inner medulla both with or without ureteral obstruction, although the production rate by the tubules was relatively low in the obstructed kidney compared to the sham-operated control. A greater production of these vasoactive compounds was noted by glomeruli from the kidneys with unilateral or bilateral obstruction and the contralateral kidney with unilateral obstruction. Glomeruli obtained from the kidney with unilateral obstruction produced more thromboxane B2 than the kidney with bilateral obstruction, and the resultant TxB2/PGE2 ratio was higher in the unilaterally obstructed kidney. This difference in the glomerular thromboxane B2 production may be responsible for the haemodynamic changes between unilateral and bilateral ureteral obstructions. An increased prostaglandin E2 production by glomeruli from the contralateral kidney with unilateral obstruction may contribute to a compensatory response.

Animals↗
PubMed1992

Ca(2+)-independent contraction of uterine smooth muscle induced by vanadate and its inhibition by Ca2+.

Vanadate, 30 microM, contracts uterine smooth muscle of estrogen-dominated non-pregnant rats in Ca(2+)-free medium after preincubation with 3 mM EGTA. In spite of the phosphorylation of the myosin light chain during this contraction, studies with fura-2 suggested that this contraction was not accompanied by an increase in the cytosolic Ca2+ level. Inhibitors of the myosin light chain kinase and protein kinase C partly inhibited this contraction. Vanadate seems to enter the cell through anion channels to inhibit phosphatases, resulting in phosphorylation via basal activities of the myosin light chain kinase and protein kinase C. An increase in the cytosolic free Ca2+ level resulted in relaxation of the contracting muscle in the same manner as in the oxytocin-induced Ca(2+)-free contraction.

Alkaloids↗
PubMed1991

[Urethral indwelling catheter, intermittent self-catheterization and urinary infection].

Once a catheter has been passed into the bladder without contamination, there are several possible routes of subsequent infection during drainage period, such as: 1. Entry of bacteria alongside the catheter in the urethra. 2. Introduced bacteria adhered easily to the indwelling catheter and drainage system and colonized. 3. The catheter tip is covered rapidly by various nutrient materials which becomes a good culture medium of stuck bacteria, which is a supply source of bacteria into the bladder urine. 4. Although the motile bacilli ascend very slowly through the stagnant tube and no bacteria ascend against a slowly moving column, rapid transport of organisms occurs in the swirling fluid caused by the passage of rising air bubbles. 5. Continuous urethral catheter drainage permits an average residual urine volume of 7.3 ml. 6. The catheter destroys the antibacterial defense mechanisms of the urinary bladder. The reasons why in many cases of intermittent self-catheterization (CID) urine becomes sterile despite non-sterile procedure, are as follows. In addition to that CIC has none of the disadvantages of the indwelling catheter, it improves the vesical defense mechanisms deteriorated by high pressure voiding. The number of bacteria reintroduced during catheterization is relatively small and they can be eradicated by usual scheduled catheterization within 4-5 hours without residual urine. CIC must be started before trabeculation or diverticuli are formed, in which bacteria remain. Actual determination of residual urine volume after catheterization will help to prescribe a rational program of CIC.

Bacteria↗
PubMed1991

[Absorption of the urinary constituents from canine ileum].

To clarify the mechanism of metabolic changes after using intestinal segments as a urinary tract, absorption of urinary constituents from the ileum was studied in dogs. An isolated distal ileum (30 cm in length) was anastomosed to the urinary bladder in each dog. Although these animals maintained the normal renal function throughout the experimental period, mild acidosis was noticed one month after anastomosis and it became severe after six months. Stagnation of a urine-like solution (artificial urine: AU) in the isolated ileum resulted in an absorption of 66% of the instilled solvent on average during 60 minutes. The average absorption rates of each AU constituent were as follows: sodium 63%, potassium 80%, chloride 83%, phosphorus 68%, magnesium 34%, urea nitrogen 93% creatinine 56%, and ammonia 97%. On the contrary, calcium increased in the stagnated fluid by 21%. In spite of the severe histologic changes in the villi of the ileal mucosa, which became atrophic and flat, no deterioration in the absorptive capacity of the AU constituents was noticed during the six month experimental period. Furosemide administration suppressed the absorption of urinary constituents, especially water and sodium. On the other hand, the absorption of urea nitrogen and ammonia was scarcely affected. Perfusion of the isolated ileum with AU (0.5 ml/min) for 60 minutes resulted in an absorption of 59% of the solvent and 50 to 86% of each constituent. The rate of absorption was reduced after increment of the perfusion rate. In conclusion, the absorption of urinary constituents occurs rapidly and significantly. The absorptive capacity remains longer regardless the severity of histological changes of the ileal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1990

[Estimation of glomerular filtration rate from the urinary excreted contrast medium concentration].

In the animal experiments, glomerular filtration rate (GFR) values were estimated from the urinary response to the intravenously administrated iopamidol. By introducing some reasonable assumptions, mass balance equations about the contrast medium were transformed and GFR was defined as the ratio of logarithm of urinary concentration by time. Urinary concentrations were determined by measuring the photodensity on the X-ray film of urine specimens. Obtained values of GFR were well fitted to those obtained by the analysis of the plasma disappearance curve. The advantage of this method is that measurement of urinary volume is not necessary.

Animals↗