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A Hishida

Publications and source records attributed to A Hishida.

At least 19 recordsLinked to original sources

Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori.

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury.

Transforming growth factor-beta (TGF-beta) plays a critical role in the progression of renal fibrosis. The activity of TGF-beta is tightly controlled by various mechanisms, among which antagonizing Smad-mediated gene transcription by co-repressors represents one of the important components. We investigated the expression, degradation, and ubiquitination of Smad transcriptional co-repressors SnoN (ski-related novel gene N) and Ski (Sloan-Kettering Institute proto-oncogene) in renal fibrogenesis. We also studied the involvement of Smad-ubiquitination regulatory factor 2 (Smurf2) in ubiquitination of SnoN protein. The kidneys of mice with unilateral ureteral obstruction (UUO) and those of sham-operated mice were used. Renal lesions and the expression of TGF-beta1, type I collagen, SnoN, Ski, and Smurf2 were examined by immunohistochemistry, Western blot, and/or real-time reverse transcriptase-polymerase chain reaction. Degradation and ubiquitination of SnoN/Ski proteins were also investigated. The obstructed kidneys of UUO mice showed progressive tubulointerstitial fibrosis, high expression levels of TGF-beta1, type I collagen, SnoN and Ski mRNAs, and low levels of SnoN and Ski proteins. Both degradation and ubiquitination of SnoN/Ski proteins were markedly increased in the obstructed kidneys, in which Smurf2 expression was increased. Smurf2 immunodepletion in extracts of obstructed kidneys resulted in reduced ubiquitination of SnoN. Our results suggest that the reduction of SnoN/Ski proteins resulting from increased ubiquitin-dependent degradation is involved in the progression of tubulointerstitial fibrosis.

Animals↗

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). AIM: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. RESULTS: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. CONCLUSIONS: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Aged↗

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status.

BACKGROUND: Famotidine increases Helicobacter pylori-eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. AIM: To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. METHODS: Twenty healthy volunteers with different CYP2C19 genotypes--consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers--underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. RESULTS: With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). CONCLUSION: Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine.

2-Pyridinylmethylsulfinylbenzimidazoles↗

High ratio of 1,25-dihydroxyvitamin D3 to parathyroid hormone in serum of tuberculous patients with end-stage renal disease.

AIM: Diagnosis of tuberculosis is sometimes difficult because of the low specificity of diagnostic procedures especially in patients on end-stage renal disease (ESRD). As abnormal vitamin D metabolism has been reported in tuberculosis, the aim of the present study was to determine whether serum concentration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may be a useful diagnostic indicator of tuberculosis in patients with ESRD. PATIENTS AND METHODS: Serum concentrations of 1,25-(OH)2D3, parathyroid hormone (PTH), and calcium were compared in 6 patients with ESRD and active tuberculosis (ESRD-TB group) and 110 patients with ESRD and no tuberculosis (ESRD group). These parameters were compared before and after treatment for tuberculosis in patients of ESRD-TB group. RESULTS: Hypercalcemia was observed in all 6 patients in the ESRD-TB group. Both higher serum concentration of 1,25-(OH)2D3 and lower serum concentration of PTH were observed in the ESRD-TB group relative to the ESRD group, suggesting enhanced extrarenal production of 1,25-(OH)2D3 and suppressed secretion of PTH by hypercalcemia in the ESRD-TB group. However, these parameters could not be used to distinguish the ESRD-TB group from the ESRD group. The ratio of 1,25-(OH)2D3 to PTH in serum was above 0.9 in the ESRD-TB group and below 0.9 in the ESRD group. Antituberculous treatment reduced this ratio to the range observed in the ESRD group. CONCLUSION: High ratio of 1,25-(OH)2D3 to PTH in serum is noted in active tuberculous patients with ESRD because of enhanced extrarenal production of 1,25-(OH)2D3.

Aged↗

Association between blood indoxyl sulfate and carbonyl stress marker in hemodialysis patients.

BACKGROUND: Indoxyl sulfate (IS) is a protein-bound solute, which is progressively retained in blood according to the decline of renal function. However, clinical relevance of excess IS in hemodialysis (HD) patients remains unknown. PATIENTS AND METHODS: We measured serum IS and clinical parameters including pentosidine, carboxymethyllysine (CML) and homocysteine levels in 55 HD patients (age: 67 +/- 2 years, time on HD: 67 +/- 11 months, male/female = 30/25), and examined the relationship between IS and these data. RESULTS: Serum IS was markedly increased in HD patients (80.49 +/- 6.17 microg/ml) compared to normal range (< 1.9 microg/ml). IS was significantly and positively correlated with time on HD (p < 0.01), blood urea nitrogen (p < 0.01), beta2-microglobulin (p < 0.03), and protein catabolic rate (PCR) (p < 0.01). The patients with increased IS needed a higher erythropoietin dosage. Blood IS was positively correlated with pentosidine (r = 0.505, p < 0.01) and CML (r = 0.275, p < 0.05). In contrast, blood IS was not associated with nutritional and inflammatory parameters. A stepwise multiple regression analysis revealed that time on HD, PCR and pentosidine were significant determinants of IS. CONCLUSIONS: Serum IS was related to time on HD and dietary protein intake. Accumulated IS may be associated with enhanced carbonyl stress in chronic HD patients.

Adult↗

A case of anaphylactoid shock induced by the BS polysulfone hemodialyzer but not by the F8-HPS polysulfone hemodialyzer.

A 57-year-old woman was admitted because of severe bradycardia and hypotension caused by an anti-arrhythmic agent and beta-blocker. For 19 months before admission, she had been undergoing hemodialysis with an F8-HPS polysulfone membrane hemodialyzer without any complications. In 2 dialysis sessions after admission, when a BS polysulfone membrane was used, she experienced anaphylactoid shock with severe hypotension leading to syncope, dyspnea and vomiting, just after the start of hemodialysis. After the anaphylactoid shock, her dialyzer membrane was changed to a cellulose triacetate membrane and she did not suffer from such attacks. This case indicates that severe anaphylactoid shock may be caused by a biocompatible dialyzer membrane and that the reactions of patients to each polysulfone membrane may differ among polysulfone membranes made by different manufacturers.

Anaphylaxis↗

Ultrasound changes of the carpal tunnel in patients receiving long-term hemodialysis: a cross-sectional and longitudinal study.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the major problems of long-term hemodialysis (HD), but sometimes difficult to distinguish from uremic or diabetic neuropathy by clinical symptoms. PATIENTS AND METHODS: To evaluate the diagnosis of CTS more precisely, we examined the ultrasonographic alterations of the carpal tunnel and tendons of 90 wrists from 45 patients undergoing HD for more than 5 years. We measured the thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel (CT), and the width of the CT, and compared those values with sensory (SCV), motor conduction velocity (MCV) of the median nerve and clinical symptoms. In addition, we longitudinally measured CT and PRL in the same patients for 5 years, and compared ultrasonographic changes and clinical parameters. RESULTS: A linear positive relationship was found between HD duration and PRL thickness (r = 0.43, p < 0.01) or CT width (r = 0.53, p < 0.01). CT diameter was negatively correlated with MCV (r = -0.30, p < 0.01) and SCV (r = -0.33, p < 0.04). PRL thickness was also inversely correlated with MCV (r = -0.44, p < 0.01) and SCV (r = -0.46, p < 0.01) of the median nerve, respectively. The wrists with clinical CTS and/or previous CTS surgery had significantly greater CT and PRL values compared to patients without CTS (CT: 6.1 0.2vs. 8.0+/-0.3 mm,p<0.01;PRL: 1.9+/-0.1 vs. 3.6 +/- 0.2 mm, p < 0.01). There was a significant increase in CT width from 6.2 +/- 0.2 to 7.1 +/- 0.2 mm (p < 0.01) and PRL thickness from 2.4 +/- 0.2 to 2.8 +/- 0.2 mm (p <0.01) during the 5-year observation, respectively. PRL thickness was constantly increased at the rate of 0.4 mm during the study. However, no significant association was found between the 5-year increases in CT and PRL distance and age, gender, the prevalence of diabetes, or laboratory parameters such as blood beta2-microglobulin, pentosidine and Kt/V(urea). CONCLUSION: Our data suggest that echographic evaluation of the wrist tissue thickness was useful to assess the progression of CTS. Serial measurements of the wrist by echography may be helpful to clarify the advance of subclinical CTS in patients receiving long-term HD.

Adult↗

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody.

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.

Adult↗

Focal segmental glomerulosclerosis in a case of panhypopituitarism: a possible role of growth hormone treatment.

Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

Adult↗

Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis.

Pseudohyperkalemia is defined as a serum potassium concentration 0.4 mEq/l greater than the plasma concentration. The basis of this phenomenon is the release of intracellular potassium from platelets, leukocytes, or erythrocytes, commonly in the setting of extreme leukocytosis (> 10 x 10(4)/microl) or thrombocytosis (> 60 x 10(4)/microl). We report a case of pseudohyperkalemia in a patient with chronic renal failure and polycythemia vera without the finding of severe leukocytosis or thrombocytosis (white blood cell count 1.88 x 10(4)/microl and platelet count 37.9 x 10(4)/microl, respectively). The serum potassium concentration was 8.2 mEq/l, while the plasma potassium level was 6.4 mEq/l in a sample obtained simultaneously. The concentrations of platelet factor IV and beta-thromboglobulin, known to be markers of platelet activation, were greater than 100 ng/ml and 200 ng/ml, respectively, indicating that platelet activation may have been related to the development of pseudohyperkalemia in this patient. These findings suggest that pseudohyperkalemia should be considered when hyperkalemia is seen in a patient with chronic renal failure and myeloproliferative disorders.

Aged↗

Dexamethasone attenuates neutrophil infiltration in the rat kidney in ischemia/reperfusion injury: the possible role of nitroxyl.

Neutrophil infiltration to the tissue, which is one of the important pathogenetic factors in ischemia/reperfusion injury, can be inhibited by glucocorticoids. The purpose of the present study was to clarify the mechanisms by which glucocorticoids inhibit neutrophil infiltration in renal ischemia/reperfusion injury in rats. Pretreatment with dexamethasone significantly attenuated the enhanced neutrophil infiltration and expression of intercellular adhesion molecule-1 induced by renal ischemia/reperfusion. Treatment with nitroxyl anion releaser known as Angeli's salt abolished the beneficial effect of dexamethasone in renal ischemia/reperfusion. Renal dysfunction and tubular damage induced by renal ischemia/reperfusion were not ameliorated by pretreatment with dexamthasone. These results indicate that the attenuation by dexamethasone of neutrophil infiltration and intercellular adhesion molecule-1 expression during renal ischemia/reperfusion may be mediated by the suppressed production of nitroxyl anion. Thus, neutrophil infiltration in renal ischemia/reperfusion injury may be mediated, at least in part, by the enhanced production of nitroxyl anion.

Animals↗

Tryptophan glycoconjugate as a novel marker of renal function.

PURPOSE: Neither serum creatinine concentration nor creatinine clearance assess renal function accurately. Serum creatinine concentration is affected by muscle mass, and the creatinine clearance overestimates the glomerular filtration rate because of tubular secretion of creatinine. The present study was designed to determine whether serum concentrations of 2-(alpha-mannopyranosyl)-L-tryptophan (MPT), a tryptophan glycoconjugate, can be used as a marker of renal function. METHODS: Clearances of MPT and of inulin were compared in normal rats and in rats with cisplatin-induced acute renal failure. We also compared the clearances of MPT and of creatinine with inulin clearance in 25 patients with chronic renal disease. Serum concentrations of MPT and creatinine as a function of MPT clearance were determined in 108 patients with chronic renal disease. RESULTS: There was strong linear correlation between clearances of MPT and inulin in rats (r = 0.97) and humans (r = 0.87), indicating that renal handling of MPT is similar to that of inulin. In humans, linear regression analyses indicated that MPT was a better indicator of inulin clearance than was creatinine clearance. At the same level of renal function, serum creatinine concentrations tended to be lower in patients with less muscle mass (as indicated by a urinary creatinine excretion <1,000 mg in 24 hours) than in those who excreted >1,000 mg in 24 hours, whereas serum MPT concentrations were not affected by creatinine excretion. CONCLUSION: MPT clearance can replace inulin clearance in the clinical setting. The serum MPT concentration is an accurate measure of renal function even in patients with diminished muscle mass, and thus is a better indicator of renal function than is the serum creatinine concentration.

Acute Kidney Injury↗

Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis.

Proteinuria in passive Heymann nephritis (PHN) results from complement-mediated glomerular injury, since complement depletion with cobra venom factor (CVF) prevents proteinuria. However, there are no comprehensive morphological studies identifying the sites of injury leading to onset of proteinuria. To address this issue, we attempted to locate sites of injury involved in the onset of proteinuria in PHN. PHN was induced in intact Munich-Wistar rats (PHN-rats, examined at days 3, 5, and 7) and in complement-depleted rats (CVF treated, PHN-CVF-rats, examined at days 3 and 5). The distribution of endogenous albumin in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli using immunogold immunocytochemistry, and glomerular anionic sites were visualized by polyethyleneimine staining. In addition, the ultrastructural localization of an epitope recognized by a proteinuria-inducing monoclonal antibody (called 5-1-6) directed against the slit diaphragm was examined. Significant proteinuria was seen in intact PHN-rats, starting at day 5. The intensity of gold labeling for endogenous albumin was significantly increased at the outermost site of the GBM (GBM interfacing foot process and the filtration slit, designated area O) at day 3 in both PHN-rats and PHN-CVF-rats in comparison to untreated controls. At day 5, labeling for albumin in area O was decreased in PHN-rats, but not in PHN-CVF-rats, where it was then higher; in PHN-rats, some areas between epithelial cells and subepithelial deposits were almost free of albumin labeling at day 7. There was no evidence of epithelial cell detachment in any group at day 5, but on day 7 limited focal detachment was seen exclusively in PHN-rats. In proteinuric rats, amorphous material that stained for albumin could be seen in the urinary space, without any exocytosis of labeling by glomerular epithelial cells. A significant reduction of intensity of staining for anionic sites was seen in parallel in both groups, but only in the regions of the lamina rara externa adjacent to subepithelial deposits. This local loss of charge might contribute to enhanced permeability to albumin in both PHN- and PHN-CVF-rats. Changes in the appearance of the filtration slits and in the density and distribution of antigen recognised by monoclonal antibody 5-1-6 were similar in PHN- and PHN-CVF-rats at day 5. Complement depletion prevented neither the reduction in anionic sites of the GBM nor the changes in the slit diaphragm observed. These data suggest that albumin leakage between the epithelial cell and the GBM (area O) could occur in PHN-rats, perhaps as a result of epithelial foot-process changes. This may be the final link in the chain of events responsible for the onset of proteinuria in PHN.

Albumins↗

Cytokines and cell cycle regulation in the fibrous progression of crescent formation in antiglomerular basement membrane nephritis of WKY rats.

Cytokines may regulate cell proliferation by cell-cycle-regulatory proteins, in which cyclin-dependent kinase inhibitors (CDKI) inhibit cell proliferation. We investigated whether CDKI p21 or p27, both of which are potentially regulated by transforming growth factor (TGF)-beta, a key cytokine in fibrogenesis, are involved together with TGF-beta and/or platelet-derived growth factor (PDGF) in the fibrous progression of glomerular crescent formation and examined the sequential change in the cell type and the cellular background of myofibroblasts in crescent formation. Crescentic glomerulonephritis (GN) was induced by i.v. injection of rabbit antirat glomerular basement membrane antiserum in WKY rats. Animals were killed 1, 2, 3 and 4 weeks after the induction of GN, and their kidneys were processed for immunohistochemical examination. After 1 week more than 85% of glomeruli showed cellular crescents, which became fibrocellular with decreased cellularity by 4 weeks. ED 1-positive macrophages were components of crescent cells in about 44% at 1-2 weeks, and this proportion declined markedly afterwards. Alpha smooth muscle actin (alpha SMA, a marker for myofibroblasts)-positive cells were found in Bowman's epithelial cells (BEP) and in some crescent cells at 1 week, becoming major components of crescent cells by 4 weeks (about 40%). It was 2 weeks before invasion of alpha SMA-positive interstitial cells into glomeruli was evident. PDGF-B and PDGF receptor beta-positive cells, indicating possible targets for PDGF, were found in BEP adjoining crescent formation almost exclusively from 1 to 2 weeks. By contrast, both TGF-beta receptor types I- and II-positive cells, indicating possible effectors for TGF-beta, were found in BEP and crescent formation, and the percentage of these in the crescent formation did not change until 4 weeks (about 32%). Cells with positive immunostaining for proliferating cell nuclear antigen and cyclin A, markers for cell proliferation, in the crescent formation peaked in number and proportion at 1-2 weeks, then decreased. In contrast, cells with positive immunostaining for p21 and p27, CDKI, were sparse at 1 week, and then increased markedly in number and in proportion, peaking at 3 (39.6%) or 2-3 weeks (about 25-30%), respectively. The present study demonstrates that restrained expression or a transient increase in p21 and p27 may be associated with proliferation or with inhibited proliferation of crescent cells, most of which are macrophages and myofibroblasts. The action, of PDGF and TGF-beta may contribute to the recruitment of myofibroblasts into the crescent. The action of TGF-beta on crescent cells might be linked to the expression of p21 and/or p27.

Actins↗

Role of atrophic tubules in development of interstitial fibrosis in microembolism-induced renal failure in rat.

We explored the origin and participation of atrophic tubules in the progression of interstitial fibrosis using a new microembolic rat model of chronic renal failure in which foci of atrophic tubules with cuff-like basement membrane thickening developed at 4 weeks. Atrophic tubules, immunoreactive for vimentin and platelet-derived growth factor, were surrounded by transformed interstitial cells expressing platelet-derived growth factor receptor beta and alpha-smooth muscle actin. Some tubules in the deep cortex and the outer stripe of the outer medulla had a mosaic appearance. Tall, intact proximal tubular cells with a brush border and positivity for Phaseolus vulgaris erythroagglutinin, adjoined typical atrophic tubule cells having no brush border and an immunostaining pattern characteristic for atrophic tubules. The transformed interstitial cells expressing alpha-smooth muscle actin were located near atrophic but not intact tubular epithelial cells. Type IV collagen accumulated between damaged tubular cells and transformed interstitial cells. Heat shock protein 47 showed immunoreactivity in damaged epithelial cells and in interstitial myofibroblasts. Staining with an anti-endothelial antibody suggested damage to peritubular capillaries near atrophic tubules. By disturbance of microcirculation following microsphere injection, proximal tubular cells expressed vimentin and platelet-derived growth factor; diffusion of the latter presumably stimulated transformation of interstitial cells to myofibroblasts. Injured tubular epithelial cells and interstitial myofibroblasts both were responsible for interstitial fibrosis.

Actins↗

Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha.

Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis. In this study, we conducted a 6 month prospective and crossover trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for renal itching. We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients. We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors (sTNFR-I, sTNFR-II) in 19 patients using hemodialysis, complicated by prolonged severe pruritus for 6 months. Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects. Serum sTNFR-II levels were significantly and negatively correlated with serum albumin (r = -0.602, p = 0.007). A significant positive relationship was also found between sTNFR-I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association was found between the degree of pruritus and circulating sTNFR-I and II values. Skin itching scale was significantly decreased from 2.7 +/- 0.2 to 2.1 +/- 0.3 following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there was no change in itching scales during 3 months of conventional therapy (2.2 +/- 0.3 versus 2.2 +/- 0.3, p = NS). PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes. These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system.

Adult↗