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Biomedical subjects

H Nihei

Publications and source records attributed to H Nihei.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Immunohistochemical analysis of the normal and cystic kidney using antibody against polycystin 2].

A second gene responsible for polycystic kidney disease(PKD) has been identified recently, and an antisera(YCC2) against this gene's product, polycystin 2, has been generated. In the present study, we investigated the normal distribution of polycystin 2 in human adult kidneys and analyzed the expression of polycystin 2 in the cystic tubules of kidneys from patients with PKD and acquired cystic disease of the kidney(ACDK). The expression of polycystin 2 in normal regions of resected human kidneys, 4 cases of autosomal dominant polycystic kidney disease(ADPKD) and 4 cases of ACDK was examined by immunohistochemically staining the specimens with a polyclonal antibody specific to the C-terminal region of polycystin 2. This region is specific to polycystin 2 and does not crossreact with polycystin 1. In normal kidneys, prominent expression of polycystin 2 was observed in the distal tubules. A faint level of expression was detected in the proximal tubules, and the glomerulus and vessels were almost negative for expression. In the cystic kidneys of ADPKD patients, 68.7% of the cystic tubules stained positively for YCC2, although partial staining was seen in 41.2% of the positive cystic tubules. Although the genetic background of the samples is unknown, the co-existence of positive and negative cysts suggest that a "two-hit" hypothesis is feasible and that the mutations are likely to be missense or in frame changes. In ACDK cysts, YCC2-positive staining was prominent in small cysts (less than 0.5 mm in diameter), which were also positive for DBA, a marker for distal tubules. In contrast, larger cysts of more than 0.5 mm in diameter which stained positive for a proximal tubule marker, Lotus T, tended to be less positively stained for YCC2. Overall, 94.5% of the cysts stained positive for YCC2, which is a much higher rate than that of PKD cysts. These results suggest that ACDK cysts may be generated by a different mechanism from that of PKD cysts.

Humans↗
PubMed2000

[The effects of ACE inhibitor treatment and ACE gene polymorphism on erythropoiesis in chronic hemodialysis patients].

Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.

Adult↗
PubMed1999

Recombinant human erythropoietin stimulates vascular endothelial growth factor release by glomerular endothelial cells.

We designed the present study to address the question of whether recombinant human erythropoietin stimulates DNA synthesis and vascular endothelial growth factor (VEGF) secretion in vitro using cultured bovine glomerular endothelial cells (GENs). Recombinant human erythropoietin dose-dependently stimulated the proliferation of GENs in culture, and this proliferative effect was inhibited by 1 microg/ml anti-VEGF antiserum. The increase in VEGF concentrations in the supernatants containing 10 U/ml rHuEpo was abolished by incubation with 10 microg/ml of anti-human rHuEPO antiserum, 0.2 microg/ml actinomycin D or 10 microg/ml cycloheximide. Taken together, rHuEpo stimulates GEN proliferation in vitro and VEGF release from these cells is associated with stimulation of RNA-dependent DNA and protein synthesis.

Animals↗
PubMed1999

Extracellular signal-regulated kinase mediates renal regeneration in rats with myoglobinuric acute renal injury.

In vitro data support that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), members of mitogen-activated protein (MAP) kinases, mediate the signal transduction pathways responsible for the cell proliferation. However, in vivo role of these MAP kinases is poorly understood. Intramuscular injection of 50% glycerol solution induces acute renal failure in rats. This injury is known as a model of rhabdomyolysis in human. To investigate the molecular mechanism of the signaling pathway in this injury, we examined the role of ERK and JNK. After the glycerol injection JNK was rapidly and transiently activated at about 4 h, while the activation of ERK was gradually increased and the levels were sustained at least to 24 h. Next, we examined the expression of cell-cycle related proteins after the glycerol injection using Western blot analysis. The levels of proliferating cell nuclear antigen (PCNA) protein as a marker for cell proliferation were induced at 2 h and significantly increased to 24 h after the injection. In addition, cyclins D1, D2, and D3 as markers for G1 phase also increased with similar time courses. To examine whether activation of ERK and/or JNK are involved in the renal regeneration after the glycerol injection, we examined the effect of genistein, which is an inhibitor of tyrosine kinase, on the activation of ERK and JNK. Administration of genistein to rats with this injury decreased the activation of ERK, but not JNK. The induction of PCNA and cyclin D1 was also prevented by this treatment. In this condition, renal function was further worsened as compared to control rats. These results provide the first evidence that ERK may be involved in the repair process of renal tubules damaged by this injury.

Animals↗
PubMed1999

Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis.

To elucidate the mechanism underlying crescentic formation, we assessed the phenotypic characterization and cell-cycle protein expression in human crescentic glomerulonephritis (CRGN). Kidney tissue specimens taken from CRGN patients (10 patients with pauci-immune type rapidly progressive glomerulonephritis (RPGN), 2 patients with Henoch-Schönlein purpura nephritis, and 1 patient with IgA nephropathy) were examined immunohistochemically. Most of the cellular components of the crescents expressed cytokeratin, whereas few cells expressed PHM-5. CD68-positive cells were minor components of cellular crescents, indicating that the major principal cellular component of the crescents is made up of cells with the parietal glomerular epithelial cell (PEC) phenotype. Additionally, serial section analysis revealed that Ki-67-positive cells in the crescents were frequently cyclin-A positive and Bcl-2 positive, but seldom cyclin-B(1) positive. Moreover, the expression of cyclin-dependent kinase inhibitor p27(Kip1) was low in the cellular crescents, despite being exclusively positive in podocytes within the same section. We concluded that the major component of the cellular crescents is made up of PECs and that apparent expression of cyclins and Bcl-2 and restrained expression of p27(Kip1) may be synergistically associated with the development of cellular crescents in human CRGN.

Amino Acid Sequence↗
PubMed1999

A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in glomeruli, and an increased concentration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this disease. METHODS: An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were analyzed by isoelectric focusing and immunoblotting. Apo E genotypes were determined by restriction fragment isotyping with HhaI. Polymerase chain reaction (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7Blue-T-vector and were sequenced. RESULTS: A novel apo E mutation was identified in this patient and his family. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E gene, causing the 18-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR-amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo E1, and this mutation was determined to be the structural basis for the apo E1 phenotype. One of two daughters was a heterozygous carrier of apo E1, although she did not have proteinuria or atherosclerotic diseases. CONCLUSIONS: Apo E1 (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclerosis. The result of this family study suggests that the occurrence of LPG may involve other genetic or environmental factors.

Adult↗
PubMed1999

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration.

BACKGROUND: Ultra-filtration failure is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD). This complication is related to histological changes of the peritoneum, i.e. severe interstitial fibrosis and microvascular sclerosis. Although their pathogenesis has not been elucidated yet, advanced glycation end products (AGEs) have been shown to accumulate in the peritoneal tissue of CAPD patients. METHODS: Peritoneal biopsy specimens from 14 CAPD patients with low ultra-filtration (n = 9) and high ultra-filtration (n = 5) capacity were immunohistochemically investigated using a monoclonal antibody against AGEs (6D12). The severity of peritoneal fibrosis, microvascular sclerosis and intensity of AGE accumulation were semi-quantitatively evaluated. Peritoneal ultra-filtration capacity was evaluated by calculating daily ultrafiltration volume per body weight (UFV/BW) and D/D0 (glucose) of the peritoneal equilibration test. RESULTS: In all patients with low ultra-filtration, AGE accumulated in the peritoneal fibrous tissue and microvascular walls. Remarkably, AGE accumulated more intensely in hyalinized fibrosis of small venular media. Extent of AGE accumulation in peritoneal interstitium and vascular walls correlated with the progression of interstitial fibrosis (rho = 0.727, P = 0.0088) and vascular sclerosis (rho = 0.915, P = 0.001). UFV/BW was inversely correlated to interstitial fibrosis (rho = -0.660, P = 0.0174), microvascular sclerosis (rho = -0.671, P = 0.0155) and microvascular AGE accumulation (rho = -0.678, P = 0.0145). CONCLUSIONS: In CAPD patients, AGE formation in the peritoneum correlates with the development of severe interstitial fibrosis and microvascular sclerosis, which is associated clinically with impaired peritoneal ultra-filtration.

Adult↗
PubMed1999

Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients.

Causative factors of uremia-associated atherosclerosis are complex. However, it is likely that atherogenic lipoproteins accumulated in plasma are involved. Remnant lipoproteins are atherogenic and are frequently observed in uremic plasma. LDL from uremic patients has been shown to be susceptible to in vitro peroxidation, suggesting that oxidized LDL (ox-LDL) could be excessively generated in those patients. No effective treatments to prevent accumulation of both atherogenic lipoproteins in dialysis patients have been published. Eicosapentanoic acid (EPA) may change synthesis and/or catabolism of remnant lipoproteins and increase stability of LDL to peroxidation by altering the fatty acid composition of lipoproteins. A prospective comparative study was conducted to assess the efficacy of EPA on metabolism of remnant lipoproteins and ox-LDL in dialysis patients using two new methods: an immunoaffinity gel separation for quantifying plasma remnant lipoproteins and an enzyme-linked immunosorbent assay for measuring plasma ox-LDL levels, a marker for in vivo LDL peroxidation. Twenty-two hemodialysis and 16 continuous ambulatory peritoneal dialysis patients with relatively high plasma levels of remnant lipoproteins and ox-LDL were randomized to either EPA or placebo. Highly purified EPA, in an ethyl-ester form (ethyl all-cis-5,8,11,14,17-icosapentanoate) with a purity greater than 91%, was administered at a dose of 1800 mg daily. Overall, 3 mo of treatment with EPA significantly reduced the levels of both remnant lipoproteins (52% reduction) and ox-LDL (38% reduction). Additionally, gel filtration chromatography of lipoproteins showed that EPA treatment concomitantly normalized other potential abnormalities in lipoproteins. Treatment compliance was good and no critical adverse effects were observed. In conclusion, EPA administration proved to be effective and safe treatment to decrease plasma remnant lipoproteins and prevent in vivo peroxidation of LDL in dialysis patients.

Administration, Oral↗
PubMed1999

Theoretical comparison of surgery and radiosurgery in cerebral arteriovenous malformations.

OBJECT: Management of patients with cerebral arteriovenous malformations (AVMs) is controversial. Excellent surgical results are obtained in patients with low Spetzler-Martin grades, whereas radiosurgery offers a good alternative with its high obliteration rate. In the absence of randomized studies, physicians must choose a treatment plan based on the currently available data. To support this decision-making process, a mathematical model designed to describe patient survival rates after each treatment option was developed. METHODS: The theoretical survival curve in patients undergoing conventional surgery, radiosurgery, or observation was calculated. Theoretical life expectancies in patients with AVMs who presented at various initial ages were calculated for each treatment strategy. A systematic method was also developed to compare the estimated risks of various treatment combinations. CONCLUSIONS: Conventional surgery and radiosurgery definitely produced better survival rates than observation. In the comparison of surgery with radiosurgery, radiosurgery was equivalent to surgery with a combined morbidity and mortality rate of approximately 7% for a 20-year-old patient with an unruptured cerebral AVM. Data for other patient ages and treatment combinations are tabulated for use in determining the best treatment strategy. The authors believe that their analysis will provide logical support for the decision-making process involved in the treatment of patients with cerebral AVMs.

Adult↗
PubMed1999

The role of protein kinase C activity in the proliferation of peritoneal fibroblasts.

OBJECTIVE: To clarify the effect of glucose on peritoneal sclerosis, we performed several experiments to determine how glucose influences the proliferation of, and the production of extracellular matrix proteins by, peritoneal fibroblasts. The effect of heparin on these phenomena was also studied. DESIGN: Using rat peritoneal fibroblasts, cells were cultured in four separate media: M199 with 5% fetal bovine serum (FBS) (control medium), control medium with 4% glucose (glucose medium), glucose medium with H7 [an inhibitor of protein kinase C (PKC)] 50 micromol, and glucose medium with heparin 50 microg/mL. Cell proliferation and concentrations of procollagen 3 peptide (P3P) and hyaluronic acid (HA) in the supernatants were evaluated at 24 hours, 72 hours, and 120 hours after culture. PKC activity in cytosolic and cell membrane fractions were measured 30 minutes after incubation in control medium and in glucose medium with and without heparin. RESULTS: Glucose accelerated cell proliferation 24 hours after culture, but inhibited it 120 hours after culture. Glucose stimulated the production of HA from these cells 72 hours and 120 hours after culture, but it did not stimulate the production of P3P at any time. Heparin and H7 inhibited cell proliferation by glucose 24 hours after culture. Heparin and H7 also inhibited the production of HA in the peritoneal fibroblasts after culture, but did not affect the production of P3P. Glucose accelerated PKC activity in cell membrane, but not in cytosol. Heparin inhibited the elevated PKC activity of the membrane fraction by glucose. CONCLUSION: Glucose may accelerate the proliferation of, and HA production in, peritoneal fibroblasts by stimulation of cellular PKC activity. Heparin suppresses these phenomena by inhibiting PKC activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Increased serum levels of vascular endothelial growth factor in human crescentic glomerulonephritis.

OBJECTIVE: To investigate the serum levels of vascular endothelial growth factor (VEGF) in human crescentic glomerulonephritis (CRGN). METHODS: The serum VEGF levels in CRGN patients were compared with those in healthy subjects and in various types of glomerulonephritis. In addition, we investigated the relationship between serum VEGF levels and creatinine levels (Scr) and pathological parameters. RESULTS: The serum VEGF levels of the CRGN patients were significantly higher than in the healthy subjects and patients with MCNS, IgAN, and FGS. No correlation was found between serum VEGF levels and Scr in the RPGN patients. The serum VEGF levels in 6 CRGN patients had significantly decreased after 6 months of corticosteroid therapy. Moreover, there was a significant correlation between the serum VEGF levels and the crescent frequency or the grade of interstitial injury, and the rates of glomerular infiltration by macrophages. CONCLUSIONS: In the CRGN patients, severe glomerular and interstitial damages would result in increased serum VEGF levels and corticosteroid therapy may exert its efficacy through reduction of serum VEGF levels.

Adrenal Cortex Hormones↗
PubMed1999

[Clinical analysis of thrombocytopenia in chronic dialysis patients].

Thrombopoietic status in dialysis patients is controversial. This study addressed this issue by analyzing factors associated with thrombopoiesis. One hundred and fifty-one dialysis patients(119 HD and 32 CAPD) and 41 age-matched control subjects were studied. Thrombocytopenia was defined as a platelet count less than 150 x 10(9)/l. Reticulated platelets(RET), a marker for marrow megakaryopoiesis, were measured using thiazole orange dye by flowcytometry. Serum thrombopoietin (TPO) level was measured by ELISA. Hepatitis C virus(HCV) antibody, platelet-associated IgG(PAIgG), and other clinical parameters were examined in the patients. The platelet counts in the HD patients were significantly lower than those in the CAPD or controls. The incidence of thrombocytopenia was 30.0% in the HD patients. Thrombocytopenia was more prominent in the HCV-infected HD patients in whom PAIgG was mostly positive(81.8%) and its titer was remarkably high(102.9 +/- 92.7 pg/ml). There were significant differences in the RET counts between patients with and without thrombocytopenia. None of the other parameters, such as iPTH, beta 2 microglobulin, and Kt/V, nor any prescribed drugs were related to thrombocytopenia. Serum TPO was significantly higher in HD patients(135.9 +/- 60.1 pg/ml) than in the controls(97.0 +/- 53.4 pg/ml). In conclusion, thrombocytopenia is frequent in HD patients, especially in HCV-infected HD patients. Reduced marrow magakaryopoiesis is mostly responsible for thrombocytopenia and peripheral destruction of platelets could be, in part, involved. Mild elevation of serum TPO possibly indicates a counter-response to decreased mass of megakaryocyte in bone marrow.

Adult↗
PubMed1999

[Relationship between renal function and morphometric assessment in chronic glomerulonephritis].

In an attempt to reveal a correlation between the degree of glomerular hypertrophy, interstitial damage, and hemodynamic parameters in chronic nephritis, the glomerular area (GA) and proportion of interstitial area (IA%) were determined quantitatively with an image analyzer, and the effective renal plasma flow (ERPF) and filtration fraction (FF) were determined simultaneously. The subjects were 12 patients with focal glomerulosclerosis (FGS) and 12 patients with IgA nephropathy (IgAN), all of whom had a similar glomerular filtration rate (GFR). The GFR was 58.6 +/- 11.4 ml/min/1.48 m2 in the FGS group and 53.9 +/- 13.1 ml/min/1.48 m2 in the IgAN group, and the difference between the two groups was not significant. On the other hand, ERPF was significantly lower and FF was significantly higher in the FGS group than in the IgAN group. GA was significantly higher in the FGS group than in the control group (10 kidney donors), and GA in the IgAN group was equivalent to that in the control group. IA% was almost equal in the FGS and IgAN groups, and significantly higher in both groups than in the control group. Although GA was not correlated with GFR in the two groups, it tended to be positively correlated with FF in the FGS group, and the correlation between GA and FF reached statistical significance when the IgAN group was combined with the FGS group. The above findings suggest that the pattern of progression of the glomeruli and interstitial lesions and of the intrarenal hemodynamics involved in them may differ in the FGS and IgAN groups. However, since ERPF significantly decreased in the FGS group, even though IA% was the same in both groups, the possibility that ERPF was functionally decreased in the FGS group cannot be ruled out.

Adult↗