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Biomedical subjects

A Hishida

Publications and source records attributed to A Hishida.

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

Role of apoptosis in uranyl acetate-induced acute renal failure and acquired resistance to uranyl acetate.

BACKGROUND: We have previously reported that animals recovering from uranyl acetate (UA)-induced acute renal failure (ARF) were resistant to subsequent insult. Recent evidence suggests that apoptosis participates in tubular damage. We investigated the role of apoptosis in UA-induced ARF and attenuation of ARF in acquired resistance to UA in rats. METHODS: ARF was induced by an intravenous injection of UA (5 mg/kg) in rats. Rats of group 1 were injected with UA and followed for 28 days. Group 2 rats were injected with a second dose of UA (5 mg/kg) 14 days after the first injection and were followed for 14 days. All rats received an intraperitoneal injection of bromodeoxyuridine (BrdU) one hour before sacrifice. Using kidneys, histologic examination and immunohistochemical detection of proliferating cell nuclear antigen (PCNA), BrdU, Bcl-2, and Bax were performed. To detect apoptosis, electron microscopy, analysis of DNA fragmentation, and the TUNEL methods were adopted. RESULTS: UA increased the number of damaged renal tubules and serum creatinine, which peaked at 5 days in group 1, but both returned to baseline values by 14 days. Apoptosis was confirmed by electron microscopy and the "ladder" pattern of DNA fragments on gel electrophoresis. The number of apoptotic tubular cells evaluated by the TUNEL method showed two peaks at days 5 and 14 in group 1. The second peak of TUNEL-positive cells was preceded by an increased number of BrdU-positive nuclei, PCNA-positive nuclei, and total number of tubular epithelial cells. Renal damage after the second UA injection was markedly reduced. The peak number of apoptotic cells in group 2 was significantly less than that in group 1. CONCLUSIONS: Two peak levels of apoptotic cells occurred in UA-induced ARF. The first peak might play a role in UA-induced tubular damage, while the second one might represent the removal of excess regenerating cells during the recovery phase. Modulation of apoptotic cell death might be involved in the acquired resistance to rechallenge injury by UA.

Acute Kidney Injury↗
PubMed2000

Vitamin D deficiency is implicated in reduced serum albumin concentrations in patients with end-stage renal disease.

The mortality rate in hemodialysis patients remains extremely high, and reduced serum albumin concentration resulting from malnutrition is the strongest predictor of mortality and morbidity. Several inflammatory cytokines involved in malnutrition, including interleukin-1, interleukin-6, and tumor necrosis factor-alpha, are modulated by 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], of which synthesis is impaired in end-stage renal disease. We evaluated whether 1,25-(OH)(2)D(3) deficiency might be involved in reduced serum albumin concentrations. Fifty-one predialysis uremic patients about to begin hemodialysis therapy were divided into groups with serum 1,25-(OH)(2)D(3) concentrations less than 18 pg/mL (low-D(3) group; n = 39) and concentrations of 18 pg/mL or greater (normal-D(3) group; n = 12). Serum albumin concentrations before the initiation of hemodialysis treatment were compared between the two groups. Furthermore, the effect of supplementation with active forms of vitamin D during 4 months of hemodialysis treatment on serum albumin concentrations was retrospectively evaluated in the low-D(3) group. Serum albumin concentrations in the low-D(3) group were significantly less than those in the normal-D(3) group (3.58 +/- 0. 50 versus 3.82 +/- 0.10 g/dL; P = 0.034). Considering all patients, a significant positive correlation between serum concentrations of albumin and 1,25-(OH)(2)D(3) was noted (r = 0.417; P = 0.0023). Supplementation with active forms of vitamin D significantly increased serum albumin concentrations in the low-D(3) group from 3. 61 +/- 0.12 to 3.79 +/- 0.13 g/dL (P = 0.0067). These findings indicate that reductions in serum albumin concentrations may be attributed, at least in part, to vitamin D deficiency in patients with end-stage renal disease.

Calcitriol↗
PubMed2000

A case with acute renal failure complicated by Waldenström's macroglobulinemia and cryoglobulinemia.

We encountered a 53-year-old man associated with acute renal failure caused by Waldenström's macroglobulinemia and type I cryoglobulinemia. Treatment with prednisolone and cyclophosphamide induced a rapid recovery from acute renal failure. Renal histology revealed endocapillary proliferation and lobular formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries which were positive for IgM on immunofluorescence study. Although the exact mechanism for pathophysiology of acute renal failure remains unknown, treatment with prednisolone and cyclophosphamide could induce a rapid recovery from acute renal failure accompanied by Waldenström's macroglobulinemia and type I cryoglobulinemia.

Acute Kidney Injury↗
PubMed2000

Immunoelectron microscopic study on type I, II and III TGF-beta receptors on visceral glomerular epithelial cells in relation to glomerular basement membrane alterations in proteinuric rats.

BACKGROUND: Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (TbetaRI) and type II (TbetaRII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo. METHODS: We examined TbetaRI, II, and III protein expression on visceral glomerular epithelial cells (GEP) in relation to GBM alterations in passive Heymann nephritis (PHN), anti-GBM nephritis and anti-thymocyte serum (ATS) nephritis. Renal tissues were examined by pre-embedding immunoelectron microscopy 3, 7 and 14 days after induction of nephritis in rats. RESULTS: In normal control rats TbetaRI was not detected on GEP, TbetaRII expression was very occasionally found on GEP and TbetaRIII was seen in the cytoplasm of the GEP. TbetaRI, TbetaRII, and TbetaRIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of TbetaRI, TbetaRII, and TbetaRIII was still similar to that of normal control rats, and GBM alterations in both models were not prominent except for deposit formation in PHN. From day 7 onwards, in both models, expression of TbetaRI and TbetaRII on GEP increased in association with GBM thickening. Expression of TbetaRIII in the cytoplasm of the GEP was increased, with occasional positive staining being seen on the urinary surface of the GEP from day 7 onwards. On the other hand, at day 3 of ATS nephritis, increased expression of TbetaRI and TbetaRII on GEP was noted, but from day 7 onwards, expression of TbetaR II on GEP dramatically decreased. Expression of TbetaRIII in the cytoplasm of the GEP also transiently increased at day 3. GBM thickening was not noted in ATS nephritis. CONCLUSIONS: The results suggest that persistent upregulation of expression of TbetaRI, TbetaRII and possibly TbetaRIII on GEP may contribute to GBM matrix accumulation in vivo.

Animals↗
PubMed2000

Low free thyroxine concentrations and deficient nocturnal surge of thyroid-stimulating hormone in haemodialysed patients compared with undialysed patients.

BACKGROUND: There is little information on the differences in pituitary-thyroid function between undialysed and haemodialysed patients. METHODS: Serum concentrations of free thyroxine (T(4)) and free triiodothyronine (T(3)), measured by enhanced chemiluminescence immunoassay, and thyroid-stimulating hormone (TSH) were compared in undialysed (n=22) and haemodialysed patients (n=85). The response of the serum TSH concentration to exogenously administered thyrotropin-releasing hormone (TRH) and circadian variation in serum TSH were also studied in the two groups. RESULTS: Serum free T(4) concentration was significantly lower in haemodialysed than in undialysed patients (1.02+/-0.02 vs 1.33+/-0.06 ng/dl, P<0.0001). Serum concentrations of free T(3) and TSH were essentially the same for the two groups. The response of serum TSH concentration to TRH was basically the same. Serum TSH concentration in undialysed patients during the night and in the morning were 142.4+/-15.4% and 121.7+/-4.1% of that during the day, the differences being significantly different. A nocturnal surge of TSH was not observed in haemodialysed patients. CONCLUSIONS: Low serum free T(4) concentration and a deficient nocturnal surge of TSH were found in haemodialysed patients compared with undialysed patients. The deficient nocturnal surge of TSH may contribute to the lower serum free T(4) concentration in haemodialysed patients.

Circadian Rhythm↗
PubMed2000

New insights on the pathogenesis of hypercalcemia in primary hyperparathyroidism.

The pathogenesis of hypercalcemia in primary hyperparathyroidism is attributed to increased calcium release from bone, increased calcium reabsorption in renal distal tubules, and increased intestinal calcium absorption. However, it remains unclear which factor is the main process. We encountered a 56-year-old woman with myasthenia gravis, in whom hypercalcemia and elevated serum parathyroid hormone (PTH) level were observed. Diagnosis of primary hyperparathyroidism was made. Treatment with methylprednisolone for myasthenia gravis was associated with a marked decrease in both biochemical markers of bone formation and resorption without any changes in endogenous cAMP and serum levels of calcium, PTH, and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. These findings suggest that the possible pathogenesis of hypercalcemia in primary hyperparathyroidism may be attributed to the increased calcium reabsorption in the kidney and the increased intestinal calcium absorption as a result of stimulated production of 1,25-(OH)2D3 in the kidney. It thus follows that the renal tubular effect rather than the skeletal effect of the PTH excess may play a pivotal role in the development of hypercalcemia in primary hyperparathyroidism.

Bone Resorption↗
PubMed2000

Cardiac autonomic neuropathy in patients with chronic renal failure on hemodialysis.

To characterize uremic cardiac autonomic neuropathy, we measured plasma catecholamines, analyzed the 24-hour heart rate variability (HRV), and acquired serial images with (123)I-metaiodobenzylguanidine (MIBG) in 44 patients with chronic renal failure on hemodialysis and in 14 controls. Time-domain measures were calculated using the Marquette HRV program. MIBG clearance rates from the heart and lung were evaluated on planar images, and the regional MIBG uptake in the left ventricular myocardium was evaluated with single-photon emission computed tomography. Compared with controls, plasma dopamine and norepinephrine levels were elevated (p < 0.001 and p = 0.03, respectively), and all the time-domain measures of HRV were reduced in the patients (p < 0.001). The MIBG clearance rate from the heart was higher (p < 0.001), that from the lung was lower (p < 0.001), and the myocardial MIBG distribution was more heterogeneous in patients than in controls (total uptake score p </= 0.03). These variables were similar between 26 patients without and 18 patients with hypertension. Uremic cardiac autonomic neuropathy may be characterized by high plasma levels of dopamine and norepinephrine, reduced HRV, and abnormal MIBG kinetics in the heart with heterogeneous myocardial MIBG distribution, suggesting cardiac sympathetic overactivity and parasympathetic deterioration. In addition, abnormal MIBG kinetics in the lung may imply pulmonary sympathetic nervous dysfunction and/or endothelial dysfunction in uremic patients.

3-Iodobenzylguanidine↗
PubMed2000

Atypical Fabry's disease presenting with cholesterol crystal embolization.

We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.

Aged↗
PubMed2000

Catastrophic exacerbation of antiphospholipid syndrome after lung adenocarcinoma biopsy.

We describe a 60-year-old man with nephrotic syndrome due to a glomerular thrombotic microangiopathy caused by the antiphospholipid syndrome (APS) associated with a lung adenocarcinoma. Although no significant aggravation of APS was noted following renal biopsy, catastrophic exacerbation of APS occurred 3 days after a lung adenocarcinoma biopsy while warfarin and prednisolone were being administered. The patient died of multiple organ failure 37 days after the lung adenocarcinoma biopsy. This case emphasizes the need for great caution for catastrophic exacerbation of malignancy associated APS following biopsy of the underlying malignancy.

Adenocarcinoma↗
PubMed1999

Prednisolone induces an increase in serum calcium concentration: possible involvement of the kidney, the bone, and the intestine.

To evaluate the early effect of glucocorticoids on calcium metabolism, 15 subjects aged 22-58 years (5 males, 10 females) with chronic glomerulonephritis were orally treated with 40 mg daily of prednisolone. Five of these subjects were diagnosed with nephrotic syndrome and none had a serum creatinine concentration of more than 1.4 mg/dl. Serum specimens and 24-hour urine specimens were obtained just before and 24 hours after a single oral dose of prednisolone. Serum calcium, ionized calcium, phosphate, intact parathyroid hormone (PTH), intact osteocalcin and 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and urinary excretion of calcium, phosphate, and deoxypyridinoline were measured. Both serum calcium and ionized calcium concentrations were significantly increased from 4.39 +/- 0. 10 to 4.47 +/- 0.09 mEq/liter (P = 0.037) and from 2.48 +/- 0.04 to 2.55 +/- 0.04 mEq/liter (P = 0.002), respectively, 24 hours following a single oral dose of prednisolone. Serum intact PTH concentration slightly decreased, but the difference was not significant by statistical analysis. Serum intact osteocalcin concentration was markedly suppressed. In contrast, no significant changes were observed in urinary excretion of deoxypyridinoline. Serum 1,25(OH)(2)D(3) concentration measured in five patients was significantly increased. No significant changes in urinary excretion of calcium was observed in the face of these findings. It thus follows that a single oral dose of prednisolone administration increases serum calcium and ionized calcium concentrations, possibly mediated by suppressed bone formation, increased intestinal absorption of calcium, and impaired urinary excretion of calcium.

Administration, Oral↗
PubMed1999

A rat model of progressive chronic renal failure produced by microembolism.

We report a new model of chronic progressive renal failure in rats, produced by a single injection of microspheres (20 to 30 micrometer in diameter) into the left renal artery after right nephrectomy. Significant proteinuria appeared after 4 weeks, followed by hypoalbuminemia and hypercholesterolemia, in rats that received approximately 5 x 10(5) microspheres (0.8 mg). Renal function partially recovered by 4 weeks after nephrectomy and injection from postoperative dysfunction, but deteriorated again 12 weeks after operation. In the early stage, histologic examination showed tubules with cuff-like thickening of basement membranes scattered among apparently intact tubules. Many epithelial cells in the atrophic tubuli were immunoreactive for proliferating cell nuclear antigen (PCNA). Dilated tubules became apparent several weeks after development of tubular atrophy, most likely representing distal tubules. Dilated tubuli were mostly negative for the proliferation marker. These results showed similarity to findings in human chronic renal failure and strongly suggested that tubular atrophy and dilation in chronic tubulointerstitial lesions differ in pathogenesis. This new model of renal failure induced by microembolism should be useful for studying the interaction between normal and diseased tissue elements in histologically heterogenous lesions as well as the pathogenesis of interstitial fibrosis in disturbance of microcirculation.

Albuminuria↗
PubMed1999

Ureteral obstruction reverses glomerular proliferation in immune complex glomerulonephritis.

We investigated an effect of ureteral obstruction on a progressive immune complex glomerulonephritis in murine lupus erythematosus. Unilateral ureteral obstruction for 8 days significantly decreased the expanded glomerular mesangial area, as measured by computer-assisted morphometry (4.44 +/- 0.33 x 10(-4) mm2 to 3.60 +/- 0.34 x 10(-4) mm2, P < .05), and reduced the staining for IgG, C3, and extracellular matrix components, whereas the nephritis was exacerbated in the contralateral non-obstructed kidney. The renal concentration of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in the obstructed kidneys 8 days after obstruction significantly exceeded that of kidneys in sham-operated controls (344.2 +/- 83.9 pg/mg tissue protein vs 50.0 +/- 27.5 pg/mg tissue protein, P < .01; 71.9 +/- 11.4 pg/mg tissue protein vs 9.5 +/- 2.3 pg/mg tissue protein, P < .01), whereas thromboxane B2 (TxB2) levels were similar in the two groups (33.9 +/- 4.5 pg/mg tissue protein vs 31.3 +/- 2.6 pg/mg tissue protein). Next, an experiment was performed to evaluate the role of renal eicosanoids in the amelioration in the immune complex glomerulonephritis after ureteral obstruction. Treatment with the cyclooxygenase inhibitor indomethacin abolished the decrease in mesangial area induced by ureteral obstruction (7.7% +/- 6.9%). CV-4151, a thromboxane synthetase inhibitor, had no effect on the decrease in mesangial area (-25.8% +/- 6.8%, P < .05). We conclude that unilateral ureteral obstruction quickly decreased the mesangial expansion in immune complex glomerulonephritis, and vasodilatory eicosanoids such as PGE2 and PGI2 at least partly contribute to the amelioration of glomerular histology.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death.

To clarify the pathophysiologic role of apoptosis in acute renal failure (ARF), we examined whether the attenuation of cisplatin-induced ARF is associated with the change in the degree of apoptotic cell death. The administration of cisplatin (CDDP) (6 mg/kg body weight) in rats induced ARF at day 5, as manifested by a significant increase in serum creatinine (Scr) and tubular damage. CDDP-induced apoptotic cell death was confirmed by electron microscopic examination, agarose gel electrophoresis, and increased cells positive for TaT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) in the outer medulla of the kidney. Treatment with dimethylthiourea (DMTU)--a scavenger of hydroxyl radicals--or glycine abrogated CDDP-induced increases in Scr, the tubular damage score, and the number of TUNEL-positive cells. Pretreatment with uranyl acetate (UA) induced a significant expression of Bcl-2 in the kidney and ameliorated CDDP-induced increases in Scr, the tubular damage score, and TUNEL-positive cells in the outer stripe of the outer medulla. Our findings indicate (1) that the attenuation of CDDP-induced ARF was associated with less apoptotic cell death and (2) that the induction of the anti-apoptotic protein Bcl-2 attenuated apoptosis and tubular damage. Our results suggest that apoptotic cell death may play an important role in the development of cisplatin-induced ARF.

Acute Kidney Injury↗
PubMed1999

Increased transforming growth factor-beta2 expression in the glomerular arteriole of the juxtaglomerular apparatus in a Bartter's-like syndrome.

Although transforming growth factor-beta (TGF-beta) has been shown to participate in regulating hormone synthesis and release, little is known about involvement of individual human TGF-beta isoforms, TGF-beta1, -beta2, and -beta3, in renin synthesis and release. We examined expression of these TGF-beta isoforms in a 50-year-old man with a Bartter's-like syndrome whose renal biopsy specimen showed hyperplasia of the juxtaglomerular apparatus (GA), mild mesangial hypercellularity, focal tubular atrophy, and interstitial fibrosis. Immunoreactivity for renin and marked expression of TGF-beta2 mRNA were noted in the glomerular arteriole of the JGA, whereas mRNA expression for TGF-beta1 was only slight and that for TGF-beta3 was still more faint. Expression of mRNAs for all 3 TGF-beta isoforms was increased in the fibrotic interstitium. This expression pattern suggests that TGF-beta2 may be involved in inducing renin synthesis and/or release in the glomerular arteriole of the JGA.

Arterioles↗
PubMed1999

Increased levels of transforming growth factor-beta in HIV-associated nephropathy.

BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) is a renal disease of unknown pathogenesis. Recent evidence suggests that the fibrogenic cytokine transforming growth factor-beta (TGF-beta) might be involved. We hypothesized that overproduction of TGF-beta in the kidney might be involved in the pathogenesis of HIVAN. METHODS: The mRNA and protein expression of TGF-beta isoforms, TGF-beta 1, TGF-beta 2, and TGF beta 3, deposition of matrix proteins induced by TGF-beta, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and -negative patients. The ability of Tat to induce production of TGF-beta and matrix proteins was also studied in human mesangial cells. RESULTS: Normal kidneys, thin basement membrane nephropathy, and minimal change disease were negative for the three TGF-beta isoforms and Tat. In HIVAN, levels of TGF-beta isoforms and Tat were significantly increased, along with the expression of TGF-beta mRNA and deposition of matrix proteins stimulated by TGF-beta. Increased levels of TGF-beta isoforms, but not Tat, were also found in other glomerular diseases characterized by matrix accumulation. HIV infection, in the absence of HIVAN, was not associated with an increase in TGF-beta or Tat expression. Tat stimulated the expression and production of TGF-beta 1 and matrix proteins by human mesangial cells. CONCLUSIONS: Our findings suggest that overproduction of TGF-beta is involved in the pathogenesis of HIVAN.

AIDS-Associated Nephropathy↗
PubMed1999

Altered abdominal fat distribution and its association with the serum lipid profile in non-diabetic haemodialysis patients.

BACKGROUND: Disturbances of lipid and carbohydrate metabolism may be associated with the distribution of abdominal adiposity. However, little is known about the alteration of abdominal adiposity and its association with the serum lipid profile in haemodialysis patients. METHODS: We evaluated the distribution of abdominal adiposity by using computed tomography and examined its relationship with the serum lipid profile in 92 non-diabetic haemodialysis patients and 80 control subjects with normal renal function. Since the mean body mass index (BMI) and total body fat mass were significantly lower in the haemodialysis patients than in the control subjects, the subcutaneous abdominal fat area and the visceral fat area were standardized by body mass index and compared between the haemodialysis patients and the control subjects. RESULTS: Mean subcutaneous fat area/body mass index (SFA/BMI) was significantly lower, and mean visceral fat area/body mass index (VFA/BMI) was significantly higher in the haemodialysis patients (SFA/BMI, 2.40+/-0.12; VFA/BMI, 2.28+/-0.15) than in the control subjects (SFA/BMI, 3.75+/-0.21, P<0.01; VFA/BMI, 1.65+/-0.15, P<0.01). Consequently, visceral fat area/ subcutaneous fat area ratio was significantly higher in the haemodialysis patients (1.05+/-0.07) than in the control subjects (0.46+/-0.04, P<0.01). A scattered plot of visceral fat area relative to BMI revealed that visceral fat area was higher in the haemodialysis patients than in the control subjects at any BMI level. A simple regression analysis showed that BMI, total body fat mass, subcutaneous fat area and visceral fat area were all associated with serum triglycerides and the atherogenic index, (total cholesterol-HDL cholesterol)/HDL cholesterol. Furthermore, a multiple regression analysis indicated that the visceral fat area was the best predictor for either the atherogenic index or triglycerides among these fat components. CONCLUSIONS: These data indicate that haemodialysis patients exhibited a visceral fat accumulation irrespective of BMI, and this shift of abdominal adiposity might be associated with disturbance of the serum lipid profile in non-diabetic haemodialysis patients.

Abdomen↗