Heat-shock proteins in animal models for acute renal failure.
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Acute Kidney Injury↗
Biomedical subjects
H Wakui
Publications and source records attributed to H Wakui.
Extramedullary megakaryoblastic tumors following an indolent phase of myelofibrosis.
A 59-year-old man developed multiple subcutaneous and bone tumors after 2 years' duration of indolent myelofibrosis. These tumors exhibited a diffuse proliferation of pleomorphic blast cells. The skeletal x-rays showed disseminated osteolysis and osteosclerosis. Blast cells obtained from the pleural effusion did not react with myeloperoxidase, sudan black B or non-specific esterase. Genotypic analysis of DNA samples at autopsy did not demonstrate rearrangements of T-cell receptor beta-chain or immunoglobulin heavy-chain genes. Frozen-section immunohistochemical studies revealed that the neoplastic cells were derived from megakaryocytic lineage. The present case represents a novel and unusual subtype of megakaryocytic neoplasm.
Bone Neoplasms↗
Streptococcal pneumoniae polysaccharide increases IgA-class antibody activity under the immunological memory of a protein antigen: two signals on experimental IgA nephropathy.
We designed the following experiment in order to clarify the factors that induce a hyper-immune state of IgA. Six-week-old Balb/c mice were immunized with bovine gammaglobulin (BGG) at 0 and 2 weeks, followed by the administration of phosphorylcholine-BGG (PC-BGG) at 3 and 5 weeks to obtain an immunological memory. At 6 weeks, we divided the mice into three groups: one was a saline group used as a control, another was a PC-BGG group used to investigate T-cell dependent antigen, and the last was a streptococcal pneumoniae polysaccharide (R36A) group used to investigate T-cell independent antigen. We compared the antibody activity in response to BGG, and glomerular immune deposition among the groups. In the control group, antibody activities did not change, and all stainings on glomerular immune deposits were negative. In the PC-BGG group, IgG-class antibody activity was significantly suppressed (p < 0.05), but IgA- and IgM-class antibodies were not affected. The intensity of glomerular deposition of IgM was level one positivity (TFS: 116.7 +/- 20.2 (mean +/- SD)). In the R36A group, polysaccharide produced significant increases (almost four times) in IgA-class and IgM-class antibody activity under the condition of immunological memory (IgA: p < 0.05, IgM: p < 0.005). The intensity of IgA was between weak and level one positivity (TFS: 60.8 +/- 6.3), but the intensity of IgM was weak positive (TFS: 36.7 +/- 10.4). This became a predominant glomerular deposition of IgA in the R36A group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Induction and intracellular localization of 90-kilodalton heat-shock protein in rat kidneys with acute gentamicin nephropathy.
BACKGROUND: We previously reported the induction of 73-kilodalton heat-shock protein (HSP73) in injured tubular epithelial cells in rat kidneys with gentamicin-induced acute renal failure. In the present study, we examined serial expression of 90-kilodalton heat-shock protein (HSP90), another major HSP, in this animal model. EXPERIMENTAL DESIGN: Sprague-Dawley rats received gentamicin (80 mg/kg/day) for 14 days and developed acute proximal tubular injury. Serial immunohistochemical localization of HSP90 was observed at both light microscopic and electron microscopic levels, using a specific antibody against HSP90. In addition, serial renal extracts were analyzed by immunoblot. RESULTS: On light microscopy, HSP90 was induced in injured proximal tubular epithelial cells and accumulated in fine granules 36 hours after the gentamicin exposure. The size and number of these granules gradually increased to Day 12 and decreased from Day 18, and the granules disappeared on Day 27. Electron microscopy showed the accumulation of HSP90 in the swollen lysosomes and the nucleoli of the injured proximal tubular epithelial cells. On serial immunoblot analysis of renal extracts, increased amounts of HSP90 were found in association with the induction of HSP90 in injured cells. Furthermore, on immunoblot of nuclear fractions from kidneys at Days 0 and 6, HSP90 was detected in the fraction at Day 6. CONCLUSIONS: These results demonstrate that HSP90 is induced in the lysosomes and the nucleoli of damaged cells during the course of gentamicin-induced acute tubular injury. HSP90 may have roles in the disposition of degenerated proteins and in the new protein synthesis for the protection and repair of target cells from gentamicin nephrotoxicity.
Acute Kidney Injury↗
IgA nephropathy associated with mild type-coagulation factor V deficiency in father and son.
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Adolescent↗
Sclerodermatous renal crisis in a patient with mixed connective tissue disease.
We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.
Acute Kidney Injury↗
Successful delivery in a pregnant women with crescentic IgA nephropathy.
A 27-year-old Japanese female developed nephrotic syndrome and impaired renal function during pregnancy. A renal biopsy performed at 21 weeks of gestation revealed crescentic IgA nephropathy. She was treated with steroid pulse therapy followed by conventional steroid therapy. Although the nephrotic syndrome was persistent, the impaired renal function did not deteriorate after the treatment. A live infant was delivered by cesarean section at 37 weeks of gestation. After the delivery, both the nephrotic syndrome and renal insufficiency improved gradually. The indications for renal biopsy and treatments for active IgA nephropathy during pregnancy are discussed.
Adult↗
Induction and altered localization of 90-kDa heat-shock protein in rat kidneys with cisplatin-induced acute renal failure.
We purified 90-kDa heat-shock protein (HSP90) from murine brains and produced a specific antibody against the protein in a rabbit. This antibody cross-reacted with rat renal HSP90 on immunoblot analysis. Using the antibody, we observed serial immunohistochemical localizations of HSP90 in rat kidneys with cisplatin-induced acute renal failure. In normal kidneys, HSP90 was mainly localized in the cytoplasm of distal tubules and collecting ducts. Twenty-four hours after the cisplatin exposure, a rapid expression of HSP90 was observed in the cytoplasm of epithelial cells in the Henle's loops (especially at the luminal side), although there was little change in these cells on light microscopy. Degenerative changes of epithelial cells appeared in the S3 segment of proximal tubules on day 3, and epithelial cell regeneration in this portion was found from day 5. On day 5, HSP90 was markedly expressed in both the cytoplasm and the nucleus of epithelial cells in the S3 segment with a granular pattern. The induced HSP90 was then accumulated in the cytoplasm of these cells on day 7 and disappeared on day 14. Immunoblot analysis of isotonic buffer-extractable renal fractions showed that there was a rapid induction of HSP90 from day 1, and that the maximum induction of HSP90 in the extract at day 5 was 6-fold that of a control. These results suggest that HSP90 plays some role related to functional abnormalities of the Henle's loops at the luminal side, and in the regeneration of damaged cells in the S3 segment of proximal tubules, during the course of cisplatin-induced acute tubular injury.
Acute Kidney Injury↗
An isoform of protein disulfide isomerase is expressed in the developing acrosome of spermatids during rat spermiogenesis and is transported into the nucleus of mature spermatids and epididymal spermatozoa.
We have purified an isoform of protein disulfide isomerase (EC 5.3.4.1) from rat liver, and raised a specific antibody against the purified protein in rabbit. Immunohistochemical studies using this antibody on rat testis sections, at both light and electron microscopic levels, showed a specific localization of the isoform of protein disulfide isomerase in the developing acrosome of the spermatids. The protein was transferred to the acrosomic vesicle from the Golgi apparatus at late Golgi phase, and remained present in the acrosome of spermatids during cap phase, acrosome phase, and maturation phase. In addition to the acrosome, the protein appeared in the nucleus of spermatids during maturation phase, and was localized in the nucleus of epididymal spermatozoa. By immunoblot analysis, almost all of the isoform of protein disulfide isomerase in the testis was found to be extractable by an isotonic buffer. On the contrary, detergent extraction was required for complete solubilization of the protein in the epididymis. These results suggest that the isoform of protein disulfide isomerase is a new intra-acrosomal soluble protein, and that the protein begins to enter the nucleus of mature spermatids in the testis and tightly binds to the nuclear components in epididymal spermatozoa.
Acrosome↗
Kidney diseases among the elderly--a clinicopathological analysis of 247 elderly patients.
We describe the clinicopathological features of 247 patients over the age of 60 with renal disorders. We acceded the histological classification of WHO recommendation, except for IgA nephropathy as primary glomerulonephritis. All nephrotic patients other than those with diabetic glomerulosclerosis (DGS) or amyloidosis were treated with steroids and/or immunosuppressants. Clinical data showed 88 patients with nephrotic syndrome. The histological study revealed that 142 patients had primary renal diseases and 105 patients had secondary renal diseases. Of 88 nephrotic patients, 35 were membranous nephropathy (MN) and 9 were minimal change nephrotic syndrome (MCNS). In secondary nephrosis, amyloidosis and DGS were diagnosed in 9 and 7 patients, respectively. A good response to therapy was obtained in MN (89%) and MCNS (78%). However, nephrotic patients with mesangial proliferative glomerulonephritis, amyloidosis, or DGS had unfavorable outcomes. Histological observations are useful aids in estimating the prognosis and therapy selection for renal disorders even in elderly patients.
Age Factors↗
Immune complex type crescentic glomerulonephritis accompanied with perinuclear anti-neutrophil cytoplasmic antibodies.
A 70-year-old male developed rapidly progressive glomerulonephritis syndrome with serum perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). A renal biopsy showed diffuse crescentic glomerulonephritis. Immunofluorescence microscopy revealed 2+ granular staining of IgG over the mesangial area and along glomerular capillary walls. Electron microscopy showed scattered deposits in the paramesangial area. These morphologic findings were consistent with those of immune complex type crescentic glomerulonephritis (IC-CGN). Serum C3, C4, and CH50 were within normal limits, and circulating immune complexes were not detected by C1q-binding assay, but both P-ANCA and anti-myeloperoxidase antibodies were positive. A possible relation of P-ANCA to IC-CGN is discussed.
Aged↗
Altered localization of 73-kilodalton heat-shock protein in rat kidneys with gentamicin-induced acute tubular injury.
BACKGROUND: The constitutive 73-kilodalton heat-shock protein (HSP73) has been shown to have various essential functions in cells under both normal and stress conditions. In the present study, we observed serial localizations of HSP73 in rat kidneys with gentamicin-induced acute tubular injury. EXPERIMENTAL DESIGN: Sprague-Dawley rats received gentamicin (80 mg/kg/day) for 14 days, and developed acute proximal tubular injury. The intrarenal immunohistochemical distribution of HSP73 was examined by using a specific antibody against HSP73. In addition, HSP73 content in both isotonic buffer- and detergent-extractable renal fractions were measured by immunoblot analysis. RESULTS: After the gentamicin exposure, HSP73 moved from the nucleus to the cytoplasm, and accumulated in granules that were considered to be expressed within enlarged lysosomes in the injured proximal tubular epithelial cells. These granules started to appear from 36 hours after the first gentamicin exposure, enlarged in size until day 12, and gradually diminished after day 18. At day 27, the HSP73 localization pattern returned to that in the normal kidney. Moreover, significantly increased HSP73 protein bands were detected by immunoblot of detergent-extractable fractions from gentamicin-treated rat kidneys at from 36 hours to day 15 after the gentamicin exposure. CONCLUSIONS: Our findings suggest that HSP73 is rapidly induced as an insoluble form in injured lysosomes of the proximal tubular epithelial cells during gentamicin-induced acute tubular injury.
Animals↗
Purification of a mature form of 60 kDa heat-shock protein (chaperonin homolog) from porcine kidney and its partial amino acid sequence.
1. We have purified a 58 kDa collagen-binding protein from a 4 M guanidine hydrochloride extract of porcine kidney. 2. This protein was identified as a mature form of 60 kDa heat-shock protein (HSP60, chaperonin homolog) based on its partial amino acid sequence. 3. Among 98 determined sequences of the porcine protein, 97 residues were identical with those deduced from nucleotide sequence of the cDNA encoding human HSP60.
Amino Acid Sequence↗
Renal localization of the constitutive 73-kDa heat-shock protein in normal and PAN rats.
We purified the constitutive 73-kDa heat-shock protein (HSP73) from the bovine brain, and produced a specific antibody against the protein in a rabbit. On immunoblotting, the antibody cross reacted only with a protein band with a molecular mass of 73 kDa in a crude extract from normal rat kidneys, which was regarded as rat renal HSP73. The intrarenal immunohistochemical distribution of HSP73 was examined by using this antibody, on both normal rat kidneys and kidneys with puromycin aminonucleoside nephrosis. HSP73 was predominantly present in epithelial cells of the glomeruli and the tubules. In normal kidneys, HSP73 was generally localized in both the cytoplasm and the nucleus of these epithelial cells, except for proximal tubular epithelial cells. On the other hand, in kidneys with puromycin aminonucleoside nephrosis, HSP73 accumulated in the cytoplasm at a level higher than in the nucleus in association with the severity of renal dysfunction and proteinuria. These findings indicate that HSP73 is mainly expressed in glomerular and tubular epithelial cells in the kidney under a physiological condition, and that its expression changes from the nucleus to the cytoplasm under pathological conditions such as a protein overload to these epithelial cells.
Animals↗
Localization of phosphoinositide-specific phospholipase C-alpha in porcine kidney.
The presence of multiple forms of phosphoinositide-specific phospholipase C (PLC), an important enzyme in the cell signal transduction, suggests that specialized functions of tissues and cells may require different modes of PLC regulation. In the present study, we have purified a 54-kDa heparin-binding protein from a 4 M guanidine hydrochloride extract of porcine kidney, and identified it as one of isoenzymes of PLC on the basis of its partial amino acid sequence. Among 194 determined sequences of the porcine protein, 186 residues were identical with those deduced from nucleotide sequence of the cDNA encoding rat PLC-alpha. The subcellular distribution of porcine renal PLC-alpha was examined by Western blotting by using a specific antibody against the purified protein. Quantitation of the Western blots revealed that 70% of PLC-alpha was membrane-associated. Immunohistochemical studies showed a specific localization of PLC-alpha in epithelial cells of distal tubules and collecting ducts of normal porcine kidney, but not in other cells composing the nephron. Moreover, the highest expression of PLC-alpha was observed in apical membranes in these epithelial cells. Thus, this form of PLC is considered to have a specific role in the signal transduction process related to regional renal tubular functions.
Amino Acid Sequence↗
Goodpasture's syndrome: a report of an autopsy case and a review of Japanese cases.
A 75-yr-old man was admitted because of acute renal failure. On the 9th hospital day, pulmonary hemorrhage occurred. He was treated with a bolus dose of methylprednisolone and plasma exchange, but died from respiratory failure on the 16th hospital day. Autopsy findings demonstrated marked intraalveolar hemorrhage and crescentic glomerulonephritis. Linear depositions of IgG along both alveolar and glomerular basement membranes (GBM) were shown by direct immunofluorescent studies. Circulating anti-GBM antibodies were demonstrated by indirect immunofluorescent techniques. This is a confirmatory case of Goodpasture's syndrome, which is rare in Japan. A review of the Japanese literature revealed some characteristics of Japanese cases.
Aged↗
Acute renal failure following hypokalemic rhabdomyolysis due to chronic glycyrrhizic acid administration.
A 72-year-old man developed acute renal failure (ARF) following severe hypokalemic rhabdomyolysis. The hypokalemia was due to chronic glycyrrhizin (glycyrrhizic acid) administration. Although glycyrrhizin-induced hypokalemic rhabdomyolysis has been occasionally reported, the association of this type of rhabdomyolysis with ARF has not been described. In the present case, there was a sensitivity to glycyrrhizin the preceding renal insufficiency, and dehydration which was thought to have contributed to ARF. It should be recognized that elderly patients with such predisposing factors may be susceptible to a rapid deterioration of renal function after glycyrrhizin-induced hypokalemic rhabdomyolysis.
Acute Kidney Injury↗
Glomerular deposition of complex-forming glycoprotein heterogenous in charge (protein HC) in IgA nephropathy.
IgA immune complexes and polymeric IgA are presumed to play important roles in the development and progression of IgA nephropathy. Complex-forming glycoprotein heterogenous in charge (protein HC), being inhibitors of neutrophilic chemotaxis, has been reported as binding to IgA. As a working hypothesis it was assumed that complexes of protein HC and IgA are present in glomeruli from IgA nephropathy patient in stable state. In this study, we examined the glomerular deposition of protein HC in 40 patients with IgA nephropathy and in 10 patients with non-IgA nephropathy. We used highly specific antibody against protein HC, that does not cross-react with alpha-1-microglobulin. An immunofluorescent study revealed that 10 out of the 40 patients (25%) showed an intensity of 1+, 16 (40%) showed weak positive (+/-), and the other 14 (35%) were negative. There was no deposition of protein HC in non-IgA nephropathy patients. Histopathological analysis demonstrated a significant correlation between the intensity of glomerular-deposited protein HC and pathological activity (p less than 0.005); the latter was defined as having either crescents in more than 15% of the remaining glomeruli (excluding global sclerotic glomeruli), or segmental necrosis or sclerosis in more than 30% of the remaining glomeruli. A significant correlation was observed between pathological activity and the intensity of deposited IgG, IgA and IgM (p = 0.01), and lambda chain (p less than 0.005). Considering anti-inflammatory activity of protein HC, these results suggest that protein HC cannot protect sufficiently acute inflammation or tissue damages due to co-deposited IgG and IgM and/or other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗