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Biomedical subjects

S Koshikawa

Publications and source records attributed to S Koshikawa.

At least 19 recordsLinked to original sources
PubMed1996

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure.

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Acute Kidney Injury↗
PubMed1995

Current status of renal replacement therapy in Japan.

The study of the current status of renal replacement therapy in Japan is based on the analysis of data from the registry reports for regular dialysis therapy and kidney transplantation. The total number of patients receiving regular dialysis therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117 (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%), nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyelonephritis (1.6%), and others. The number of kidney transplant patients in Japan was 8,384 at the end of 1991: 6,154 (73.4%) received a living donor transplantation and 2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis, 41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse polycystic kidney disease, and 66.6% for chronic pyelonephritis. The causes of death of dialysis patients were heart failure (31.1%), cerebrovascular accident (13.6%), infectious diseases (11.3%), malignancies (7.1%), cachexia/uremia (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of dialysis patients was increased in cases of less than 4 hours of the average length of each dialysis session, less than 4% and more than 9% of the average weight loss during each dialysis session, less than 1.0 of Kt/V, and less than 0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient and graft survival rates of kidney transplant patients since 1964 were 82.7% and 60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6% in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates were superior in cases treated with combined steroid, cyclosporine and azathioprine or mizoribine, to those treated with other immuno-suppressive regimens, and they decreased as the number of HLA-A, -B and -DR increased.

Actuarial Analysis↗
PubMed1995

Endothelin-1 and endothelin B type receptor are induced in mesangial proliferative nephritis in the rat.

We studied whether endothelin-1 (ET-1) and its receptor subtypes (ETAR, endothelin A type receptor; and ETBR, B type receptor) were up-regulated in the glomerulus of a rat model of mesangial proliferative glomerulonephritis induced by anti-thymocyte serum (anti-Thy-1 GN). A marked increase in preproET-1 mRNA could be demonstrated in glomerular RNA 3 and six days after disease induction (4.1- and 4.9-fold vs. day 0, respectively), corresponding to the time of mesangial cell proliferation, to the time of macrophage infiltration into glomeruli, and also to the time of increase in glomerular PDGF B-chain mRNA expression. The localization of ET-1 protein in the mesangial area and along the inner aspect of the glomerular capillary wall was also demonstrated by immunohistochemistry from day 3 and maximal at day 6. The major source of the cells expressing ET-1 in glomeruli appeared to be mesangial cells, glomerular endothelial cells and monocyte/macrophages. Furthermore, both gene and protein expression of ET-1 were associated with increased urinary excretion of ET-1. There was no increase in the plasma ET-1 immunoreactivity. Glomerular expression of ETBR mRNA increased in anti-Thy-1 GN (1.5-fold vs. day 0 at day 3 after disease induction, 3.6-fold at day 6 and 2.7-fold at day 10), but there was minimal change in ETAR mRNA expression. These results suggest that preproET-1 mRNA, which is induced in anti-Thy-1 GN, is linked primarily with ETBR mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of membrane characteristics on cytokine production by mononuclear cells in regular haemodialysis patients.

To determine the relationship between haemodialysis and cytokine production, the effects of solute permeability and biocompatibility of dialysis membranes on cytokine production by mononuclear cells were evaluated. Eighteen stable haemodialysis patients were divided into three groups and underwent haemodialysis under the same conditions except for the dialysis membrane used. Endotoxin in dialysate remained at concentrations of 10 pg/ml or less throughout the study. Haemodialysis was performed for a total of 6 weeks. Group A used a regenerated cellulose low-flux membrane during the first 2 weeks, a regenerated cellulose high-flux membrane during the next 2 weeks and a polymethylmethacrylate (PMMA) high-flux membrane during the last 2-week period, while Group B used the regenerated low-flux cellulose membrane first, followed by the PMMA low-flux membrane and PMMA high-flux membrane. Group C used the same membrane throughout the 6-week study period. Peripheral mononuclear cells were sampled before, 30 min after the start and upon completion of the final dialysis session and incubated for 18 h in the presence and absence of lipopolysaccharide (LPS) stimulation. Tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6 concentrations in the supernatant and cell lysate were determined. In all groups, cytokine production just before the final dialysis using each membrane was comparable regardless of the presence or absence of LPS stimulation. LPS-stimulated TNF-alpha production decreased significantly 30 min after the start of dialysis compared to the predialysis baseline. This change was not affected by the type of membrane used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relative hypoparathyroidism in hemodialysis patients.

To clarify the incidence and contributing factors of hypoparathyroidism in a hemodialysis (HD) population, 224 patients undergoing maintenance HD were investigated. They were divided into 4 groups according to their high-sensitive parathyroid hormone levels: extra-high (EH) group > 420,000 pg/ml; high (H) group 20,000-420,000 pg/ml; moderate (M) group 4,500-20,000 pg/ml; low (L) group, < 4,500 pg/ml. In group L, a 25-mg/kg deferoxamine (DFO) infusion test was undertaken to estimate aluminum (Al) accumulation. The distribution in each group was 42, 35, 12, and 11% for groups L, M, H and EH, respectively. Group-L patients were relatively older than those of the other groups. Diabetes was seen in 20% of group-L patients, as opposed to no diabetes in groups H and EH. Among the 22 diabetics, 82% were in group L. 70% of group-L patients showed a less than 50-micrograms/l Al increment after the DFO infusion test. Bone mineral density (BMD) did not differ between the groups with relative hypoparathyroidism (RHP=L) and background-matched non-RHP, either at the initiation of HD or the recent period, and the changes in BMD were comparable between the 2 groups. These results suggest that a considerable number of HD patients show RHP. Diabetes, but not Al accumulation, was considered to be one of the predisposing factors of RHP. Though the outcome of RHP will be aplastic bone disease (ABD) in HD patients, the clinical significance of ABD has not been fully evaluated. Further studies are required to clarify the precise mechanisms of RHP and the significance of ABD.

Adult↗
PubMed1995

Effects of rHuEpo on cellular proliferation and endothelin-1 production in cultured endothelial cells.

BACKGROUND: Although elevation of blood pressure is considered to be the main adverse effect under rHuEpo therapy in haemodialysis patients, the precise mechanism remains obscure. The direct effect of rHuEpo on endothelial cells (EC) has been suggested as one of contributing factors of rHuEpo-induced hypertension. METHODS: EC were incubated with various concentrations of rHuEpo (0, 1000, 5000, 10,000 mU/ml) for up to 7 days, and cell numbers, DNA and protein synthesis by EC and supernatant concentrations of immunoreactive endothelin-1 (ET) were determined by haemocytometer, 3H-thymidine and 3H-leucine incorporation, and RIA, respectively. The effect of rHuEpo on EC proliferation was confirmed by anti-rHuEpo rabbit antiserum. The effect of cycloheximide or acinomycin D was also examined on the increase in ET production by rHuEpo. RESULTS: rHuEpo dose-dependently stimulated the proliferation of cultured EC, and this proliferative effect was inhibited by anti-rHuEpo rabbit antiserum. DNA and protein syntheses by EC were also increased by rHuEpo. The supernatant concentrations of ET cultured with rHuEpo at 5000 mU/ml or more showed significantly greater values than those without rHuEpo and the increase in ET in the supernatants of media containing 5000 mU/ml rHuEpo was inhibited by incubation with 0.2 microgram/ml actinomycin D or 10 micrograms/ml cycloheximide. Further, rHuEpo increased DNA synthesis by EC which had been cultured in E-BM medium containing 0.5 or 2% FBS for 3 h and which were recultured in E-BM medium containing 5% FBS for 15 h. CONCLUSIONS: rHuEpo directly stimulates EC proliferation as a competence factor, and it also accelerates endothelin-1 production in association with stimulation of DNA and protein syntheses by EC.

Animals↗
PubMed1994

Immunochemical study of epidermal growth factor in rats with mercuric chloride-induced acute renal failure.

Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 +/- 0.15 versus 3.78 +/- 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 +/- 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 +/- 2.12 versus 4.84 +/- 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 +/- 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues in ARF.

Acute Kidney Injury↗
PubMed1994

[Anticoagulant effect of a single bolus injection of parnaparin sodium (LHG) on a hemodialysis model in dogs].

Hemodialysis was performed on dogs, following intravenous bolus injections of LHG at dosage levels of 50, 100 and 200 IU/kg and heparin at the levels of 100 and 200 IU/kg. LHG exerted dose-dependent anticoagulant effects and prolonged the hemodialysis time, compared to heparin with similar anti-Xa activity. When LHG was administered, the half-life of plasma anti-Xa activity was longer than that of heparin at similar anti-Xa activity. LHG prolonged the activated partial thromboplastin time (APTT) linearly and dose-dependently. However, the prolongation was much less than that of heparin, and the anticoagulant activity of LHG continued even after the APTT returned to the value before LHG administration. When LHG was administered, whole blood Xa activated coagulation time (XCT) and plasma Xa activated coagulation time (PXCT) were prolonged in a significantly greater degree compared to APTT. Therefore, XCT and PXCT were considered to be appropriate parameters for monitoring LHG. In the groups administered with LHG at 100 and 200 IU/kg, where hemodialysis could be continued for 8 hr, the tissue factor pathway inhibitor (TFPI) activity in the plasma tended to show a sustained increase. These findings suggested the possibility that not only the antithrombin III dependency mechanism but also the TFPI mechanism contributed to a longer LHG hemodialysis duration compared to heparin administration.

Animals↗
PubMed1994

Effect of dialysis membranes and ACE inhibitor on bradykinin levels during hemodialysis.

The effects of dialyzer membrane material and concurrent angiotensin converting enzyme (ACE) inhibitor on plasma bradykinin levels during hemodialysis were investigated. Six patients treated with an ACE inhibitor and 6 other patients not receiving an ACE inhibitor underwent three consecutive hemodialysis sessions with an AN-69 dialyzer and three sessions with a polysulfone dialyzer. The sequence of dialyzers (AN-69 followed by polysulfone or the reverse) was determined randomly. With the AN-69 membrane dialyzer, the plasma bradykinin level at the dialyzer outlet was significantly greater than that at the dialyzer inlet at 5 min but not at 10 min after initiation of dialysis, whereas no significant difference between inlet and outlet bradykinin concentrations was observed at either time with the polysulfone membrane dialyzer. The changes in plasma bradykinin level in patients with concurrent ACE inhibitor did not differ from those found in patients without ACE inhibitor. These results indicate that the AN-69 membrane stimulates bradykinin production at the initial stage of hemodialysis in patients with as well as without concurrent ACE inhibitor. Further study is necessary to clarify the exact role of ACE inhibitor in elevation of bradykinin levels during hemodialysis.

Anaphylaxis↗
PubMed1994

A multicenter study with once a week or once every two weeks high-dose subcutaneous administration of recombinant human erythropoietin in continuous ambulatory peritoneal dialysis.

OBJECTIVE: To investigate the effectiveness of administering relatively high doses of r-HuEPO subcutaneously once a week or once every 2 weeks in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Multicenter prospective analysis. The trial was divided into two phases: an initial 8-week phase (once a week dosing) followed by a 12-week maintenance phase (once every 2 weeks dosing). A response was defined as a change in hematocrit (Ht) of 3% or more. Results were analyzed using Sheffe's test, Mantel-Haenszel's test, and Dunnett's test. SETTING: Eleven renal units in Japan providing a CAPD program. PATIENTS: Forty-one CAPD patients with a Ht of 28% or less. RESULTS: After the initial 8 weeks, 13 (81.3%) of 16 patients showed a response to 6000 U (106.9 +/- 20.0 U/kg) subcutaneously (sc), once a week. Eleven (84.6%) of 13 in the 9000 U (166.5 +/- 27.7 U/kg) group and all 12 (100%) in the 12,000 U (210.7 +/- 42.1% U/kg) group also showed responses. At the end of both phases, that is, at 20 weeks, 7 (53.8%) of 13 patients in the 6000 U group with once every 2 weeks dosing, 7 (63.6%) of 11 in the 9000 U group, and 10 (90.9%) of 11 in the 12,000 U group maintained responses with the same dosing interval. There were no significant changes in mean blood pressure during the study period, and only 2 patients developed treatable hypertension with mild headache. CONCLUSION: Administration of relatively high doses of r-HuEPO to CAPD patients once a week or once every 2 weeks is safe and potentially an effective regimen for the correction of renal anemia.

Adult↗
PubMed1993

Urinary epidermal growth factor levels in patients with acute renal failure.

To investigate the importance of epidermal growth factor (EGF) in patients with renal dysfunction, urinary human EGF (hEGF) levels were determined by radioimmunoassay in 16 patients with acute renal failure (ARF) and in 12 healthy controls. Seven patients with chronic renal failure also were studied. Urinary hEGF levels, corrected for urine creatinine concentrations, were significantly decreased in patients with ARF in the acute phase compared with normal control subjects (0.98 +/- 0.20 v 13.74 +/- 1.18 ng/mg creatinine, P < 0.001), and subsequently increased during the recovery phase (6.10 +/- 0.73 ng/mg creatinine, P < 0.001 v acute phase). A significant positive correlation existed between urinary hEGF levels and creatinine clearance in patients with ARF (r = 0.66, P < 0.001). Serum hEGF levels also were significantly lower in patients with ARF compared with normal control subjects (0.10 +/- 0.01 v 0.30 +/- 0.03 ng/mL, P < 0.001). No significant correlation was found between hEGF concentrations in serum and urine. In conclusion, measurement of urinary hEGF may be useful in the diagnosis of ARF and for following the recovery of the kidney after severe tubular injury.

Acute Kidney Injury↗
PubMed1993

Recent progress in management of secondary hyperparathyroidism of chronic renal failure.

Recent progress in cellular and molecular biology has had a great impact on our understanding of parathyroid hormone-vitamin D physiology and of the pathogenesis of secondary hyperparathyroidism in chronic renal failure and made possible the development of new therapeutic approaches for management of bone disease in dialysis patients. Management of parathyroid hyperplasia by calcitriol pulse therapy is one example. Suppression of parathyroid hyperfunction by other vitamin D analogues was also proposed, and some of these analogues are now under clinical trial. Further, percutaneous ethanol injection into hyperplastic parathyroid glands under ultrasonographic guidance has become the choice practical procedure under certain clinical settings and can be an effective alternate to surgical parathyroidectomy. In this article, we review selected and pertinent progress in the pathogenesis and management of secondary hyperparathyroidism and parathyroid hyperplasia, major causes of morbidity in chronic dialysis patients, emphasizing the important contributions made by laboratory research and critical clinical observations.

Animals↗
PubMed1993

Primary glomerulonephritis with predominant mesangial immunoglobulin G deposits--a distinct entity?

Six cases of primary glomerulonephritis with predominant IgG deposits in the mesangium are described on the basis of a review of renal-biopsy-proven 1,116 cases with primary glomerulonephritis between 1977 and 1990. All patients were female (6-52 years old). Six patients appeared with microscopic hematuria: 3 with episodes of gross hematuria and 3 with mild proteinuria, but none with the nephrotic syndrome. Renal function was normal except for 1 case (52 years old) complicated with hypertension. Serum levels of immunoglobulins and complements were almost normal. Morphologically minor or focal/segmental glomerular alterations were observed. Immunofluorescence showed that pure mesangial IgG deposition was characterized in all cases, whereas no IgA nor IgM was found in any of them. Mesangial deposition of C3 and C1q was observed in 4 and 3 cases, respectively. Electron microscopy revealed dense deposits within the mesangial area in all cases. The clinical course was benign, and the complication with systemic diseases like a rheumatic disease was not observed. This primary glomerulonephritis is an entity characterized by low incidence in Japan, mild abnormalities in urinalysis, minor glomerular alterations with predominant mesangial IgG deposits and a relative benign course.

Adolescent↗
PubMed1993

Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding.

107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.

Aged↗
PubMed1993

The distribution of 3H-labeled endotoxin in the kidney of liver cirrhotic rats.

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with 3H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of 3H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.

Animals↗
PubMed1993

Endotoxin-induced acute tubular necrosis in cirrhotic rats.

In order to clarify the role of endotoxin in acute tubular necrosis in liver cirrhosis, lipopolysaccharide (LPS) was injected to rats with liver injury with exposure to carbon tetrachloride (CCl4) inhalation. Rats showed liver cirrhosis with ascites retention after 10 weeks' CCl4 treatment and liver fibrosis after 6 weeks' CCl4 treatment. Histopathological grading of kidney injuries after LPS treatment was more severe either in cirrhotic rats or in liver fibrotic rats than in normal rats. All cirrhotic rats had severe acute tubular necrosis after either dose of LPS, but only small necrotic foci of tubuli were seen in a few normal and liver fibrotic rats. The results indicate that endotoxin, which overflows due to disturbance of inactivation in the cirrhotic liver, may contribute to acute tubular necrosis. This effect of endotoxin is supposed to be a direct hemodynamic damage.

Animals↗