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Biomedical subjects

Sachiyo Suita

Publications and source records attributed to Sachiyo Suita.

At least 37 records · Page 2Linked to original sources

Decrease in hepatic circulation induces hepatic fibrosis in a neonatal piglet model with short bowel syndrome.

BACKGROUND: Regarding the complications associated with short bowel syndrome (SBS), progressive liver failure is one of the most severe complications known to occur: Although several studies have suggested that many factors interactively influence this clinical condition we investigated the relationship between hepatic circulation and hepatic fibrosis using a neonatal piglet SBS model. MATERIALS AND METHODS: This study used the following 4 groups of neonatal piglets: a group with an 80% resection of the small bowel (SBS group), a group with a bypass operation of the small bowel (functional SBS group), a group with only a laparotomy as a sham operation (sham group), and a no operative treatment group (control group). We measured the hepatic circulation just before and after the reconstruction of the intestine, as well as on the 7th and 14th postoperative day. In addition, both blood and hepatic tissue samples were collected to investigate them both biochemically and morphologically. RESULTS: Regarding the biochemical liver function and the tissue blood flow of liver, there were no significant differences among all groups on any investigated days. However, on both the 7th and 14th postoperative days, the portal venous flow in the SBS group was significantly lower than that in other groups. According to a histological analysis, only hepatic samples on the 14th postoperative day showed mild hepatic fibrosis in the SBS group. Regarding the alpha-smooth muscle actin staining findings that expresses active stellate cells, numerous positive cells were found to be distributed in the perisinusoidal space on the 14th postoperative day in the SBS group. CONCLUSION: Based on our data, a decrease in the hepatic circulation, especially in the portal venous flow, after a massive resection of the intestine may cause progressive liver dysfunction because of the activation of hepatic stellate cells.

Animals↗

In utero exposure to mono-n-butyl phthalate impairs insulin-like factor 3 gene expression and the transabdominal phase of testicular descent in fetal rats.

PURPOSE: Phthalate esters have been shown to cause undescended testes (UT) in rats. It has been proposed that Leydig insulin-like factor 3 (INSL3) may play an important role in testicular descent. The aim of this study was to investigate the effect of mono-n-butyl phthalate (MBP) on both the INSL3 gene expression and the transabdominal testicular descent in rats. METHODS: On the 19th gestational day, the male fetuses that had been exposed to MBP on the 15th to 18th gestational days were dissected and the degree of testicular ascent was examined. Next, quantitative reverse transcriptase polymerase chain reaction was performed to analyze the testicular INSL3 gene expression. At 60 days of age, the testicular position was recorded in the rest of MBP-treated male offspring. RESULTS: On the 19th gestational day, INSL3 messenger RNA expression was significantly decreased in the MBP-treated testes, and the associated degree of testicular ascent was significantly higher than in the controls. At 60 days of age, 12 (54.5%) of 22 rats had either unilateral or bilateral UT. CONCLUSIONS: Prenatal MBP may inhibit the INSL3 gene expression associated with the transabdominal testicular ascent in fetal rats, thereby causing UT in postnatal offspring.

Animals↗

Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy.

OBJECTIVE: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic beta-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic beta-cell ATP-sensitive potassium channel. PATIENTS AND METHODS: In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. RESULTS: We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). CONCLUSION: The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations.

ATP-Binding Cassette Transporters↗

Immune tolerance induced by donor antigen and cyclophosphamide in rat fetal small bowel transplantation.

BACKGROUND/PURPOSE: Donor specific immune tolerance is thought to be the ideal state for the recipient after organ transplantation. The administration of donor antigens and cyclophosphamide has been reported to induce donor specific immune tolerance in heart or liver transplantation. However, the effectiveness of this method for small bowel transplantation has not yet been studied. We assessed the cyclophosphamide induced immune tolerance on rat fetal small bowel transplantation. METHODS: Lewis rats (RT1(1), n=99) were used as recipients while either F344 (RT1(1), n=44) or WKAM (RT1(u), n=47) rats were used as donors. The combination of F344 and Lewis rats produces an immunologically low responder, while that of WKAM and Lewis rat produces a high responder. Bone marrow and spleen cells were harvested from the donor rats and 3x10(8)/kg of each were administrated to the recipient rats intravenously on day 0. Next, cyclophosphamide was given either divisionally or bolously. The fetal small bowel of the same strain as the donor was transplanted into the rectus muscle of the recipient abdominal wall on day 10. On day 17, all grafts were taken out and graft survival was thereafter evaluated. The body weight of recipient was also assessed. RESULTS: Most of the grafts (87.5%) survived in the F344-Lewis rat (low responder) combination using the divisional administration of 120 mg/kg of cyclophosphamide. Histologically, most of them showed the whole layers of the intestinal architectureto be well preserved. The weight loss of the recipient was minimal after divisional administration. In contrast, no graft survived in the WKAM-Lewis rat (high responder) combination. CONCLUSIONS: Immune tolerance is considered to be induced by the administration of donor specific antigen and cyclophosphamide in an immunologically low responder combination. Therefore, this method is expected to be useful as an adjuvant therapy and may also be able to reduce the dose of immunosuppressive agents in living-related clinical small intestinal transplantation.

Animals↗

Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the beta-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10,431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.

Cell Cycle Proteins↗

Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma.

BACKGROUND: The amplification of the MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of MYCN remains controversial. To reassess the clinical implications of MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses. METHODS: Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 23 samples were analyzed for MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method. RESULTS: Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 46 samples showed MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of MYCN-amplified cells. The cases of MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [P <.0001], nonmass screening [P =.0003], advanced stage [P <.0001], diploid or tetraploid [P <.0001], and a Shimada unfavorable histology [P <.0001]). MYCN gene dosages of more than 2.0 were significantly associated with a high expression of MYCN (P =.0459). However, the expression level of MYCN was not significantly associated with any other prognostic factors. CONCLUSIONS: Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of MYCN amplification. In this highly sensitive analysis, MYCN amplification (MYCN/p53 > or = 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of MYCN does not appear to be an independently significant prognosis factor.

Child↗

Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma.

Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in children. Some reports have discussed the altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma; however, variable frequencies of occurrence have been noted. In the current study, among 72 cases of rhabdomyosarcoma, the authors evaluated for the expression of p53, MDM2, p16, p21/WAF1, p27, cyclin D1, cyclin E, pRb and E2F-1 protein immunohistochemically and assessed for proliferative activities using MIB-1. We also analyzed the mutation of the p53 gene in 45 cases, the amplification of the MDM2 gene in 18 cases and the mutation of the H-ras gene in 29 cases, using formalin-fixed paraffin-embedded materials. Furthermore, we assessed the correlation between clinicopathologic factors and the results of both immunohistochemical and molecular analyses. Alveolar type affected older patients, and it had a significantly higher mitotic rate compared with the embryonal type (P=0.0226). p53 overexpression was detected in 22 (30.6%) of 72 cases, and 10 (22.2%) of 45 cases had p53 gene abnormalities. As for MDM2, its overexpression was found in nine (12.5%) of 72 cases, and three (16.7%) of 18 cases showed MDM2 amplification. A statistically significant association was observed between immunoreaction for MDM2 and p53 overexpression (P=0.0002), and p53 and MDM2 overexpression was significantly correlated with high MIB-1 labeling indices. E2F-1 labeling indices showed a significantly higher score in alveolar type compared with that seen in embryonal type (P=0.0334), but MIB-1 did not. In conclusion, our study suggests that p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity in the current study. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. The current study is the first report of the correlation of E2F-1 with alveolar rhabdomyosarcoma.

Adolescent↗

Quantitative study of pulmonary endocrine cells in fetal, postnatal and adult sheep.

Using light microscopic immunohistochemistry, neuron-specific enolase (NSE)-positive endocrine cells were quantitatively analyzed in the sheep lung during different stages of development from the canalicular stages to adulthood. In all stages, NSE-positive endocrine cells were usually located in the bronchi and bronchioles as solitary cells, although a few NSE-positive cell clusters, the so-called neuroepithelial bodies, were found in some places. The number of NSE-positive endocrine cells decreased with advanced stages of gestation. In the late alveolar stage, the number of NSE-positive endocrine cells reached its bottom during the fetal period. There was a gradual upturn after birth. The overall pattern of growth and differentiation of the endocrine cells is most likely species-related and depends on the state of airway development; the number of the endocrine cells of almost all animals, excluding the sheep, in relation to the size of the lung reaches a peak in the late fetal and early neonatal periods and decreases shortly thereafter. NSE-positive endocrine cells were also predominantly located in the large airways during the early stage of development (canalicular stage), and were found more frequently in the small peripheral airways towards the term. These results show the number of NSE-positive endocrine cells in the sheep to be different from that seen in other species.

Age Factors↗

[A study of the difference in intestinal adaptation between the residual jejunum and the ileum in rats with short bowel syndrome].

OBJECTIVES: Controversy remains regarding which residual segment, namely the jejunum or ileum, is more beneficial for intestinal adaptation in patients with short bowel syndrome (SBS). The aim of our study is to evaluate the residual intestinal adaptation after a massive small intestinal resection and thereby determine which of the two residual segments demonstrates a better intestinal adaptation. METHODS: The SBS rats underwent about a 70% resection of either the jejunum or ileum, respectively. Sham rats underwent an ileal transection with a subsequent reanastomosis of the same portion. The body weight was measured every day after the operation. Two weeks after the operation, all rats were sacrificed. The intestinal length, the hematological and serum chemical data, and the histological findings of the residual intestine were investigated in all rats to evaluate the intestinal adaptation. RESULTS: The body weight gain in the rats with the residual ileum (ileum group) was similar to that of the Sham group and better than that of the rats with residual jejunum (jejunum group). The length of the residual intestines in the jejunum group was longer than that in both the sham and ileum groups. Regarding hematological and serum chemical studies, the jejunum group tended to demonstrate more anemia and malnutrition than both the sham and ileum groups. In a histological study, the villous height in both the jejunum and ileum groups was significantly larger than in the preoperative condition. In both groups, the degree of crypt depth only significantly increased in the ileum group in comparison to the preoperative condition. Regarding the thickness of the muscular layers, a no difference was observed among all groups. CONCLUSION: Based on our data, in patients with SBS, the use of the residual ileum was therefore found to be preferable to that of the residual jejunum regarding intestinal adaptation.

Adaptation, Physiological↗

Efficacy of real-time monitoring to determine motility in porcine small intestinal transplantation.

Orthotropic small intestinal transplantation (SIT) was performed in outbred 20 pigs. The interdigestive motor patterns were evaluated using strain gage (SG) force transducers. Seven pigs without SIT were treated as control (C) group. Based on the obtained data, the group, which could be detected the migrating motor complex (MMC) in the graft and alive with adequate oral feeding, was regarded as functional graft (FG) group, whereas the group which had available data recorded within 10 days before the death due to rejection was regarded as rejection (R) group. The MMC was analyzed using following parameters: duration; amplitude; and interval. In group FG, all parameters were almost same as group C, thus suggesting that the allograft in group FG had a normal motor function. In contrast, all parameters in group R were significantly lower than those in group FG, suggesting that the motility in group R was impaired. The SG method could monitor the real-time motility and was efficient for detecting the rejection of SIT.

Anastomosis, Surgical↗

Effect of a nucleoside/nucleotide-free diet in rat allogenic small intestinal transplantation.

The aim of this study is to estimate the effect of nucleoside (NS) and nucleotide (NT) on the recipient and graft immune response after rat allogenic small intestinal transplantation. Seven-week-old Lewis rats were randomly assigned to two groups, including the NS/NT free group ( n=6) and the NS/NT supplemented group ( n=6), according to the diet received. The recipient Lewis rats were each given diet for 12 days, and then, on the nineteenth day of gestation, a 2 cm jejunum from the donor fetal Fischer rat was transplanted into the abdominal wall of the recipient rats using a non-vascular anastomotic technique. The recipient rats were killed on day 2 after transplantation, and then the recipient plasma interleukin-2 (IL-2) level was measured. In addition, the histological findings of the graft were analyzed. The IL-2 level of the NS/NT free group was significantly lower than that of the NS/NT supplemented group. In order to determine the grade of rejection, the morphological findings were blindly graded on a scale of 0-4. The mean grade of the NS/NT free group was also significantly lower than that of the NS/NT supplemented group. The NS/NT free diet is therefore considered to have an immunosuppressive effect on rat allogenic small intestinal transplantation based on the recipient plasma IL-2 levels and the histological findings of the grafts.

Abdominal Wall↗

Expression of a MYCN-interacting isoform of the tumor suppressor BIN1 is reduced in neuroblastomas with unfavorable biological features.

PURPOSE: Amplification of the MYCN proto-oncogene is strongly correlated with poor outcome in neuroblastoma (NB), although deregulated MYCN is a potent inducer of apoptosis. BIN1 (2q14) encodes multiple isoforms of a Myc-interacting adaptor protein that has features of a tumor suppressor, including the ability to inhibit Myc-mediated cell transformation and to promote apoptosis. We hypothesized that BIN1 may function as a suppressor gene in NB, because Bin1 is highly expressed in neural tissues and binds the Myc Box motifs that are conserved in MycN. EXPERMENTAL DESIGN: Expression of MYCN, total BIN1, and BIN1 isoforms were determined in 56 primary NBs using the real-time PCR. Expression was correlated with biological and genetic features. To determine the functional significance of BIN1 expression we ectopically expressed BIN1 isoforms in NB cell lines with and without MYCN amplification, and assessed clonogenic growth. RESULTS: Four predominant BIN1 isoforms resulting from alternative splicing of exon 12A (a neural tissue-specific exon) and exon 13 (a Myc-binding domain encoding exon) were variably expressed in the 56 primary NBs. Expression of BIN1 was lower in: NBs with MYCN amplification (n = 10) compared with those without, P < 0.03; in International Neuroblastoma Risk Group high-risk NB (n = 19) compared with low- or intermediate-risk NB, P < 0.01; and in metastatic NB (n = 21) compared with localized NB, P < 0.06. BIN1 inactivation by deletion or genomic rearrangement was identified infrequently. Forced expression of BIN1 isoforms containing the Myc-binding domain (with or without exon 12A) inhibited colony formation in NB cell lines with MYCN amplification (P < 0.01) but not in those without. Forced expression of BIN1 isoforms with a MBD deletion did not inhibit colony formation in any cell line assessed. CONCLUSIONS: These data support that reduced BIN1 expression contributes to the malignant phenotype of childhood NB. As we reported previously, BIN1 may function to circumvent MycN-mediated apoptosis in NBs with MYCN amplification.

Adaptor Proteins, Signal Transducing↗

Dose-dependent effect of phthalate ester on testicular descent in pre-and post natal rats.

Mono-n-butyl phthalate (MBP) was administered to pregnant rats from the 15th to the 17th gestational day to investigate the dose-dependent effect of phthalate ester on testicular descent in both pre- and postnatal rats. Thirty pregnant rats (280-330 g) were separated into five groups and administered 1.0 g/kg/day MBP in group I, 0.5 g/kg/day in group II, 0.25 g/kg/day in group III, 0.125 g/kg/day in group IV from the day 15 to 17 of gestation. The rats in group V were only administered solvent and acted as controls. The position of the testis was evaluated in both pre- and postnatal rats. This was significantly higher in 20-day old fetuses in groups I and II than in groups III, IV or V. After birth, the incidence of undescended testis was also higher in groups I and II compared with those of groups III, IV or V. The undescended testes were located in the abdominal cavity in groups I and II, whereas they were located at the inguinal region in group III. The lowest dose that induced an adverse effect on testicular descent was 0.25 g/kg/day. In conclusion, maternal MBP inhibited testicular descent in prenatal rats and thus dose-dependently induced undescended testes postnatally. High-doses of MBP are thus considered to inhibit the transabdominal descent of the testis, probably due to its estrogenic activity, whereas low-doses of MBP may act as an anti-androgen and thereby inhibit inguinoscrotal testicular descent in postnatal rats.

Animals↗

Cortisol and cytokine responses after surgery in different age groups of pediatric patients.

We investigated the cortisol and cytokine responses to surgical stress in the different age groups of pediatric patients. This study included 19 neonates (0-6 days old, group I), 19 infants (1-11 months old, group II), and 20 pre-school children (1-5 years old, group III), undergoing major thoracic and abdominal surgery. We obtained blood samples preoperatively and 0, 3, 6, 12, and 24 h postoperatively to measure the plasma levels of C-reactive protein (CRP), cortisol, interleukin (IL)-6, and IL-10. The plasma CRP level in each group reached a peak value on postoperative day 2; however, the peak value was significantly lower in group I than in groups II or III (I vs II, III; p=0.0134, p=0.0017, respectively). The plasma cortisol level in each group reached a peak value just after surgery; however, the peak value was also significantly lower in group I than in groups II or III (I vs II, III; p<0.001, p=0.0104, respectively). The plasma IL-6 level in each group reached a peak level hours postoperatively; however, the peak values in groups I and II were higher than in group III (I, II vs III; p=0.003, p=0.0458, respectively). The plasma IL-10 level in each group reached a peak value just after surgery and did not differ among the three groups. The endocrine and cytokine responses to the surgical stress vary among the different age groups of pediatric patients.

Age Factors↗

Dominant beta-thalassemia with hemoglobin Hradec Kralove: enhanced hemolysis in the spleen.

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.

Adult↗

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia-II.

Morphometric analyses of the immunohistochemical expression of surfactant apoprotein A (SP-A) were carried out on the bronchioles of human congenital diaphragmatic hernia (CDH) neonates and then compared with those in a gestational and postnatal age-matched control group. There was no difference in SP-A expression between lung specimens of the control group and unaffected lungs in the CDH group. However, compared with both these lungs, the ipsilateral lungs of the CDH group showed a significant increase in SP-A expression, namely, the number of SP-A-positive cells per bronchiole, the number of SP-A-positive cells per unit perimeter of bronchiole, and the number of SP-A-positive cells per unit bronchiolar surface area. These results suggest that in lungs of CDH cases, especially ipsilateral lungs, there is a possible delay in the functional maturation or development of SP-A synthesis by the bronchiole, and this retardation may play a role in the postnatal respiratory insufficiency observed in CDH patients.

Analysis of Variance↗

Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report.

FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.

Acidosis, Renal Tubular↗