WWOX, the tumour suppressor gene affected in multiple cancers.

WWOX is a tumour suppressor gene affected in multiple cancers, especially in breast, prostate and ovary. This gene is located at the chromosomal area 16q23.3-24.1, which was identified as a common chromosomal fragile site FRA16D. WWOX turned out to possess tumour suppressor features despite the fact that the most basic (classical) way of tumour suppressor gene inactivation involves both alleles (e.g. through deletions, point mutations and promoter methylation), which is very rare event in a case of WWOX, occurring only in few cell lines. A large number of papers corroborate the phenomenon of correlation between the loss of WWOX expression and more aggressive/worse prognosis in many different types of tumours, for example breast cancer, nonsmall cell lung cancer, bladder cancer, gastric cancer or sporadic meningiomas. Ectopically increased WWOX expression promotes migration through basal membrane, however suppresses anchorage independent growth and induces normal-like colony formation in matrigel.

Responding to hypoxia: lessons from a model cell line.

Mammalian cells require a constant supply of oxygen to maintain adequate energy production, which is essential for maintaining normal function and for ensuring cell survival. Sustained hypoxia can result in cell death. It is, therefore, not surprising that sophisticated mechanisms have evolved that allow cells to adapt to hypoxia. "Oxygen-sensing" is a special phenotype that functions to detect changes in oxygen tension and to transduce this signal into organ system functions that enhance the delivery of oxygen to tissue in various organisms. Oxygen-sensing cells can be segregated into two distinct cell types: those that functionally depolarize (excitable) and those that do not functionally depolarize (nonexcitable) in response to reduced oxygen. Theoretically, excitable cells have all the same signaling capabilities as the nonexcitable cells, but the nonexcitable cells cannot have all the signaling capabilities as excitable cells. A number of signaling pathways have been identified that regulate gene expression during hypoxia. These include the Ca2+-calmodulin pathway, the 3'-5' adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, the p42 and p44 mitogen-activated protein kinase [(MAPK); also known as the extracellular signal-related kinase (ERK) for ERK1 and ERK2] pathway, the stress-activated protein kinase (SAPK; also known as p38 kinase) pathway, and the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. In this review, we describe hypoxia-induced signaling in the model O2-sensing rat pheochromocytoma (PC12) cell line, the current level of understanding of the major signaling events that are activated by reduced O2, and how these signaling events lead to altered gene expression in both excitable and nonexcitable oxygen-sensing cells.

Chelerythrine rapidly induces apoptosis through generation of reactive oxygen species in cardiac myocytes.

The role of protein kinase C (PKC) inhibition in cardiac myocyte apoptosis has not been well understood. We investigated the mechanism, by which chelerythrine, a commonly used PKC inhibitor, induces potent myocyte death. Chelerythrine (6-30 microm) rapidly induced pyknosis, shrinkage and subsequent cell death in cardiac myocytes. Chelerythrine-induced myocyte death was accompanied by nuclear fragmentation and activation of caspase-3 and -9, while it was prevented by XIAP, suggesting that the cell death is due to apoptosis. Higher concentrations of chelerythrine caused necrotic cell death where neither cell shrinkage nor caspase activation was observed. Intravenous injection of chelerythrine (5 mg/kg) also increased apoptosis in adult rat hearts in vivo. Downregulation of the phorbol 12-myristate 13-acetate (PMA)-sensitive PKC failed to affect chelerythrine-induced apoptosis, while anti-oxidants, including N-acetyl-L-cysteine (NAC) and glutathione, inhibited it, suggesting that generation of reactive oxygen species (ROS) rather than inhibition of PMA-sensitive PKC mediates chelerythrine-induced cardiac myocyte apoptosis. Chelerythrine caused cytochrome c release from mitochondria, which was significantly inhibited in the presence of NAC, suggesting that ROS mediates chelerythrine-induced cytochrome c release. Partial inhibition of cytochrome c release by Bcl-X(L) significantly reduced chelerythrine-induced apoptosis. These results suggest that chelerythrine rapidly induces cardiac myocyte apoptosis and that production of ROS, possibly H(2)O(2), and subsequent cytochrome c release from mitochondria play an important role in mediating chelerythrine-induced rapid cardiac myocyte apoptosis.

Hypoxia-induced regulation of MAPK phosphatase-1 as identified by subtractive suppression hybridization and cDNA microarray analysis.

Subtractive suppression hybridization was used to generate a cDNA library enriched in cDNA sequences corresponding to mRNA species that are specifically up-regulated by hypoxia (6 h, 1% O(2)) in the oxygen-responsive pheochromocytoma cell line. The dual specificity protein-tyrosine phosphatase MAPK phosphatase-1 (MKP-1) was highly represented in this library. Clones were arrayed on glass slides to create a hypoxia-specific cDNA microarray chip. Microarray, northern blot, and western blot analyses confirmed that MKP-1 mRNA and protein levels were up-regulated by hypoxia by approximately 8-fold. The magnitude of the effect of hypoxia on MKP-1 was approximately equal to that induced by KCl depolarization and much larger than the effects of either epidermal growth factor or nerve growth factor on MKP-1 mRNA levels. In contrast to the calcium-dependent induction of MKP-1 by KCl depolarization, the effect of hypoxia on MKP-1 persisted under calcium-free conditions. Cobalt and deferoxamine also increased MKP-1 mRNA levels, suggesting that hypoxia-inducible factor proteins may play a role in the regulation of MKP-1 by hypoxia. Pretreatment of cells with SB203580, which inhibits p38 kinase activity, significantly reduced the hypoxia-induced increase in MKP-1 RNA levels. Thus, hypoxia robustly increases MKP-1 levels, at least in part through a p38 kinase-mediated mechanism.

Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?

PURPOSE: We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction. MATERIALS AND METHODS: Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-beta and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides. RESULTS: Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-beta1 than unobstructed kidneys (79.1 +/- 8.3 versus 33.6 +/- 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 +/- 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 +/- 5.4 versus 2.2 +/- 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 +/- 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 +/- 3.4 versus 3.9 +/- 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 +/- 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac. CONCLUSIONS: The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-beta, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.

Tranilast ameliorates renal tubular damage in unilateral ureteral obstruction.

PURPOSE: We determined whether tranilast, the anti-allergic agent N-(3, 4-dimethoxyciannamoyl)-anthranilic acid, would diminish renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction and concomitantly affect renal tubular apoptosis and proliferation in that condition. MATERIALS AND METHODS: Tranilast (150 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and each day thereafter. Kidneys were harvested day 14 after unilateral ureteral obstruction. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. RESULTS: TGF-beta bioassay showed that obstructed kidneys in controls contained significantly higher mean TGF-beta plus or minus standard deviation than unobstructed kidneys in controls (73.7 +/- 13.6 versus 14.1 +/- 5.5 pg./mg. tissue) and tranilast significantly decreased tissue TGF-beta in obstructed kidneys (15.9 +/- 4.8 pg./mg. tissue). The terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay demonstrated that obstructed kidneys in controls had significantly more mean tubular apoptosis than the unobstructed counterparts (36.6 +/- 6.7 versus 5.8 +/- 5.5 nuclei per high power field) and tranilast significantly decreased mean renal tubular apoptosis in obstructed kidneys (16.2 +/- 1.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that obstructed kidneys in controls had significantly more mean renal tubular proliferation than unobstructed kidneys (20.7 +/- 3.4 versus 6.2 +/- 2.1 per high power field) and tranilast significantly increased proliferating renal tubules in obstructed and unobstructed kidneys (26.5 +/- 8.3 and 14.5 +/- 3.4 per high power field, respectively). Control obstructed kidneys exhibited significantly more fibrosis, which was also blunted by tranilast. CONCLUSIONS: Tranilast significantly decreases tissue TGF-beta, resulting in a reduction in tubular apoptosis and an increase in tubular proliferation. This finding suggests that tranilast is a promising agent for preventing renal tubular damage in unilateral ureteral obstruction.

Identification of hypoxia-responsive genes in a dopaminergic cell line by subtractive cDNA libraries and microarray analysis.

Transplantation of dopamine-secreting cells harvested from fetal mesencephalon directly into the striatum has had limited success as a therapy for Parkinson's disease. A major problem is that the majority of the cells die during the first 3 weeks following transplantation. Hypoxia in the tissue surrounding the graft is a potential cause of the cell death. We have used subtractive cDNA libraries and microarray analysis to identify the gene expression profile that regulates tolerance to hypoxia. An improved understanding of the molecular basis of hypoxia-tolerance may allow investigators to engineer cells that can survive in the hypoxic environment of the brain parenchyma following transplantation.

Glycogen synthase kinase 3beta regulates GATA4 in cardiac myocytes.

Inactivation of glycogen synthase kinase 3beta (GSK3beta) is critical for transcription of atrial natriuretic factor (ANF) by beta-adrenergic receptors in cardiac myocytes. We examined the mechanism by which GSK3beta regulates ANF transcription. Stimulation of beta-adrenergic receptors induced nuclear accumulation of GATA4, whereas beta-adrenergic ANF transcription was suppressed by dominant negative GATA4, suggesting that GATA4 plays an important role in beta-adrenergic ANF transcription. Interestingly, GATA4-mediated transcription was markedly attenuated by GSK3beta. GSK3beta physically associates with GATA4 and phosphorylates GATA4 in vitro. Overexpression of GSK3beta suppressed both basal and beta-adrenergic increases in nuclear expression of GATA4, whereas inhibition of GSK3beta by LiCl caused nuclear accumulation of GATA4, suggesting that GSK3beta negatively regulates nuclear expression of GATA4. The nuclear exportin Crm1 reduced nuclear expression of GATA4, and the reduction was enhanced by GSK3beta but not by kinase-inactive GSK3beta. Leptomycin B, an inhibitor for Crm1, increased basal nuclear GATA4 and suppressed GSK3beta-induced decreases in nuclear GATA4. These results suggest that GSK3beta negatively regulates nuclear expression of GATA4 by stimulating Crm1-dependent nuclear export. Inhibition of GSK3beta by beta-adrenergic stimulation abrogates GSK3beta-induced nuclear export of GATA4, causing nuclear accumulation of GATA4, which may represent an important signaling mechanism mediating cardiac hypertrophy.

The molecular basis of O2-sensing and hypoxia tolerance in pheochromocytoma cells.

Hypoxia is a common environmental stimulus. However, very little is known about the mechanisms by which cells sense and respond to changes in oxygen. Our laboratory has utilized the PC12 cell line in order to study the biophysical and molecular response to hypoxia. The current review summarizes our results. We demonstrate that the O2-sensitive K(+) channel, Kv1.2, is present in PC12 cells and plays a critical role in the hypoxia-induced depolarization of PC12 cells. Previous studies have shown that PC12 cells secrete a variety of autocrine/paracrine factors, including dopamine, norepinephrine, and adenosine during hypoxia. We investigated the mechanisms by which adenosine modulates cell function and the effect of chronic hypoxia on this modulation. Finally, we present results identifying the mitogen- and stress-activated protein kinases (MAPKs and SAPKs) as hypoxia-regulated protein kinases. Specifically, we show that p38 and an isoform, p38gamma, are activated by hypoxia. In addition, our results demonstrate that the p42/p44 MAPK protein kinases are activated by hypoxia. We further show that p42/p44 MAPK is critical for the hypoxia-induced transactivation of endothelial PAS-domain protein 1 (EPAS1), a hypoxia-inducible transcription factor. Together, these results provide greater insight into the mechanisms by which cells sense and adapt to hypoxia.

Cold water swim stress increases the expression of neurotensin mRNA in the lateral hypothalamus and medial preoptic regions of the rat brain.

Stress-induced analgesia is a well-documented phenomenon that occurs in all mammalian species. Forced cold water swim produces a type of stress-induced analgesia that is independent of mu opioid receptors. The neuropeptide neurotensin (NT) has been implicated in mu opioid-independent analgesia (MOIA), but the circuitry of this system is largely unknown. The medial preoptic area (MPO) and lateral hypothalamus (LH) are two regions that are known to modulate pain processing. These two regions also contain neurotensinergic projections to the periaqueductal gray, a region that has been shown to produce MOIA upon injection of NT. The goal of this study was to determine if cold water swim (CWS) stress, which produces MOIA, activates the NT-ergic systems in these two regions. In situ hybridization results indicate that CWS increases the level of NT mRNA within neurons in the MPO and LH, suggesting that these two regions are activated during this process.

[Immunohistochemical study of p53 and Ki-67 overexpression in grade 3 superficial bladder tumor in relationship to tumor recurrence and prognosis].

PURPOSE: The major drawback of the current treatment for superficial bladder tumor is the high rate of recurrence. Especially, the tumor with grade 3 component has a tendency to recur and progress in stage. However, we have difficulty in predicting tumor recurrence and stage progression accurately by conventional clinicopathological factors. We evaluated the efficacy of p53 and Ki-67 overexpression as a predictor of recurrence or prognosis in patients with superficial bladder tumor of grade 3. MATERIALS AND METHODS: Samples were obtained from 41 patients with superficial transitional cell carcinoma of the bladder of grade 3 who were treated by transurethral resection (TUR). The immunohistochemical study was performed using the antibodies against the p53 protein and Ki-67 antigen on formalin-fixed, paraffinembedded tissue specimens from initial tumors. We evaluated the correlation between these results and several clinicopathological factors. RESULTS: The p53 index and the Ki-67 index in pTa, pT1a and pT1b tumors were 26.4 +/- 30.1%, 28.6 +/- 30.0%, and 34.6 +/- 32.6% (p53) and 20.5 +/- 22.5%, 20.0 +/- 29.3%, and 29.2 +/- 28.4% (Ki-67). There was no significant difference between the each index and tumor stage. Eighteen cases (43.9%) had intravesical recurrence. The p53 index of the initial tumor from the tumor free cases (n = 23), recurrent cases without stage progression (n = 12), and stage progression cases (n = 6) were 19.7 +/- 28.2%, 42.0 +/- 28.7%, and 42.5 +/- 32.0%. Between the recurrence-free cases and the recurrent cases without progression, the p53 index of the initial tumor had statistical significance (p < 0.05). The Ki-67 index was shown to be the same pattern as the p53 index, but there was not statistical significance. Four of patients with stage progression had tumor progression within six months. Three of the patients with tumors with stage progression died of the cancer. In multivariate analysis, tumor multiplicity (p = 0.01), BCG intravesical instillation (p = 0.04), p53 index (p = 0.01) and Ki-67 index (p = 0.02) were the positive risk factors for tumor recurrence, but only the p53 index was the positive risk factor for prognosis fo the patients (p = 0.03). CONCLUSION: These results suggest that the immunohistochemical study of p53 overexpression is a useful predictor for tumor recurrence and prognosis in patients with superficial bladder tumor with grade 3.

Inverted papilloma arising in a juvenile.

A 15-year-old man presented with painless, gross hematuria. Excretory pyelography showed a filling defect in the bladder and ultrasonography revealed a solitary bladder tumor. Cystoscopy showed a solitary, papillary tumor on the bladder neck. Transurethral resection was then performed and histological examination showed an inverted papilloma. In addition, the expression of proliferative cellular nuclear antigen and p53 in the surgical specimen were 37.1 and 0%, respectively. Since an inverted papilloma arising during the first two decades of life is quite rare, we herein report the above case and review previous reports.

Generation of self-pumped phase conjugation from the -c face of BaTiO3 with femtosecond pulses.

We demonstrate a new configuration of self-pumped phase conjugation in BaTiO(3) with 450-nm femtosecond pulses. The pump beam enters the -c face of the crystal at an acute angle with respect to the +c axis. This geometry is different from all known geometries of self-pumped phase conjugations in BaTiO(3). Phase-conjugate reflectivity of 1.7% and a rise time of approximately 24 s are obtained at an average pump power of 10 mW. The ability of the phase conjugator to serve phase distortions correctly is demonstrated. We propose that the femtosecond phase conjugator operate with the hologram mechanism sharing as the double phase conjugator. The self-pumped phase-conjugate pulses are analyzed by femtosecond electric-field cross correlation.

Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure.

The present study was undertaken to verify the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen partial pressure. Diastolic PBP were employed as pulmonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m2 (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased preload and improved arterial blood oxygen partial pressure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.

Spatial-Frequency Response of Photorefractive Phase Conjugators with Ce:BaTiO(3).

We propose and demonstrate an interferometric method to measure thespatial-frequency response of photorefractive phase conjugators withCe:BaTiO(3). Two coherent beams are incident on a crystaland form an interference pattern inside the crystal. The two beamsundergo stimulated photorefractive backscattering, which creates theircorresponding phase conjugations. Then the four waves interactwithin the crystal. The spatial-frequency resolution of the phaseconjugators is measured to be as high as 3750 line pairs/mm by use ofthe interferometric method. There are several factors that limitthe measured spatial resolution when using a U.S. Air Force ResolutionChart. The output modulation deviates from the input modulation forhigh spatial frequencies. In the presence of a strong additionalpump beam, the output modulation of the phase conjugators is almost thesame as the input modulation for a wide range of input spatialfrequencies. The phase conjugator exhibits a large dynamic range ofintensity. We analyze theoretically the modulation transferfunction of photorefractive phase conjugators withCe:BaTiO(3) for two mutually coherent beams. Thetheoretical analysis is in agreement with the experimental resultswithin a small incident-angle region.

Insulin degradation by Madin-Darby canine kidney cells expressing the insulin receptor.

Prior studies have shown that Madin-Darby canine kidney cells (MDCK) overexpressing the human insulin receptor bind and respond normally to insulin (T.C. Yeh, R.A. Roth, Diabetes 43 (1994) 1297-1303). Moreover, the insulin receptor preferentially localizes to the basolateral membrane of these cells. In the present studies, insulin was added to either the apical or the basolateral side of these cells and the extent of degradation of the insulin was assessed. Radioactive insulin added to either side was bound to its receptor and the radioactivity which reached the other side of the cell was to a large extent degraded fragments. Insulin added to the apical side was degraded to a larger extent (83%) than when added to the basolateral side (49%) although the basolateral side has much more insulin receptors than the apical side. This degradation process was not inhibitors of either lysosomal enzymes, the proteasome complex or cathepsins. The degradation process could however, be potently inhibited by the sulfhydryl alkylating agent N-ethylmaleimide. Further, cell surface biotinylation study showed that the insulin degrading enzyme was preferentially localized on the apical membranes. These results suggest that insulin added on the apical side of MDCK cells are more closely linked to the degradation process than that added on the basolateral side.

[Chinese herbs nephropathy in the Kansai area: a warning report].

In 1993, Vanherweghem and his associates reported cases of rapidly progressive renal interstitial fibrosis in young women who were administered a slimming regimen including Chinese herbs. Subsequently, similar cases have been reported. In Japan, especially in the Kansai area, several cases of Chinese herbs nephropathy have already been reported. We experienced a patient suffering from Chinese herbs nephropathy (CHN), and further detected aristolochic acids from the Chinese herbs taken by the patient. Aristolochic acids are known to be causative agents of CHN. The danger of CHN should be noted as soon as possible and drugs containing aristolochic acids should be prohibited.

Overexpression of insulin degrading enzyme: cellular localization and effects on insulin signaling.

To investigate the role of insulin degrading enzyme (insulysin, EC 3.4.24.56) in insulin signaling, Chinese hamster ovary cells overexpressing the human insulin receptor were genetically engineered to also stably overexpress the rat insulin degrading enzyme. In comparison to the parental cells, these cells expressed 2.7-fold elevated levels of enzyme and insulin degradation was also increased 2-fold. These cells also exhibited a more rapid decrease in receptor tyrosine phosphorylation after removal of insulin. Moreover, low concentrations of insulin were less effective at stimulating proliferation of the cells overexpressing the enzyme. Finally, a fraction of the overexpressed enzyme as well a fraction of the endogenous enzyme could be detected on the plasma membrane surface of these cells. These results support the hypothesis that this enzyme may function in insulin signaling by degrading the insulin molecule.

[Traditional remedy-induced Chinese herbs nephropathy showing rapid deterioration of renal function].

A 19-year-old female was referred to our hospital for azotemia and anemia. She had been taking a health food for atopic dermatitis for about three years. Urinalysis showed proteinuria, glycosuria and microscopic hematuria. Generalized aminoaciduria was observed. Moreover, severe anemia, azotemia, hypokalemia and hypophosphatemia were also observed. Renal biopsy specimen disclosed hypocellular interstitial fibrosis and degeneration of the proximal tubular epithelial cells. No remarkable changes were observed in the glomeruli. Aristolochic acid was detected in the health food. From these findings, she was diagnosed as having Chinese herbs nephropathy (CHN). Although consumption of the food intake was stopped, her renal function deteriorated rapidly. Previously, we reported that certain kinds of Chinese herbal drugs contain aristolochic acid and that the drugs should be prohibited if aristolochic acid is identified. However, we experienced a patient of CHN arising from traditional remedy, which was not proved to be safe. It should be awared that health foods may contain aristolochic acid.