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BRCA1 is strongly associated with the breast cancer. BRCA1 associates with numerous proteins that repair DNA damage. Fanconi Anemia (FA) is a rare autosomal recessive disorder. It has been shown that BRCA1 regulates one of FA proteins, called FANCD2, by a process called ubiquitination. However, exactly how the FA proteins and BRCA1 interact to regulate DNA damage repair obscure. In this project, we hypothesize that BRCA1 ubiquitination of FANCD2 is affected by association with the FANCA protein complex and by association with DNA damage when embedded in chromatin. Specific aims are that (1) does BRCA1 monoubiquitinate FANCD2 in vivo using purified ubiquitination factors? (2) Do embedding FA proteins in chromatin affect their function as ubiquitination substrates? (3) Is the ubiquitination of FA proteins by BRCA1 affected by binding to damaged DNA? During the first year of grant, we purified the FANCD2, FANCA and BRCA1/BARD1 from baculovirus-infected insect cells and we identified that BRCA1 could ubiquitinated FAND2, dependent on the E2 enzymes. Also, we found direct DNA binding activity of the FANCD2 protein. Now we are trying to know the function of FANCD2 and modified FANCD2 (ubiquitinated FANCD2) on DNA or chromatin. Finally, we are trying to understand the relationship between BRCA1 and FANCD2 in the DNA damage repair pathway by keeping this project.

Previously, we showed that monensin, Na+ ionophore, potently inhibited the growth of acute myelogenous leukemia and lymphoma cells. Here, we investigated the antiproliferative effect of monensin on human myeloma cell lines. Monensin significantly inhibited the proliferation of myeloma cell lines examined with IC50 of about 1 micro M. Cell cycle analysis indicated that monensin induced a G1 and/or a G2-M phase arrest in these cell lines. To address the mechanism of the antiproliferative effect of monensin, we examined the effect of this drug on cell cycle-related proteins in NCI-H929 cells. Monensin decreased the levels of CDK2, CDK6, cdc2, cyclin A, cyclin B1, cyclin D1 and cyclin E proteins but did not alter CDK4 protein. While p21 was increased by monensin, p27 was not. In addition, monensin markedly enhanced the binding of p21 with CDK6 and cdc2. Furthermore, the activities of CDK2- and CDK6-associated kinases were reduced in association with hypophosphorylation of Rb protein. The activity of cdc2-associated kinase was decreased, which was accompanied by reduction of cdc25C phosphatase. Also, monensin induced apoptosis in myeloma cells, as evidenced by annexin V binding assay and flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with down-regulation of Bcl-2, loss of mitochondria transmembrane potential (Deltapsim) and an increase of caspase-3 activity. In addition, monensin caused the up-regulation of ERK and p38 kinase activities. Taken together, these results have demonstrated for the first time that monensin potently inhibited the proliferation of human myeloma cell lines, especially NCI-H929 cells, via cell cycle arrest in association with p21 and apoptosis.

Background/Purpose: Anal canal duplication (ACD) is the most distal and the least frequent digestive duplication. A review of the English-language literature found 15 cases reported in the pediatric age group. Methods: A retrospective chart review was performed for our experience from 1999 to 2001 with 6 patients who presented with a midline postanal opening. Results: All of 6 patients were girls and included one set of twins. Patients were from 3 to 9 months of age at the time of diagnosis (mean, 4.5 months). The anal canal duplication was delineated clearly by contrast study of the tract. All were tubular structures, 10 to 12 mm in length. None of the patients had any other associated anomalies. Five of 6 patients underwent operation between the ages of 3 and 8 months (mean, 5.4 months). Excision of the ACD was accomplished through the posterior sagittal approach. The orifice of the ACD, measuring 1 to 2 mm in diameter located just behind anus, directed to the lumen of the anal canal by keeping in the midline and ended blindly 5 mm above the dentate line without luminal communication. Histology findings showed a squamous epithelium with smooth muscle bundles in 2 cases and pseudostratified columnar epithelium with focally squamous epithelial lining and adjacent smooth muscle bundles in 3 cases. The postoperative courses were uneventful with satisfactory anal function. One patient has not yet undergone operation and has been well on outpatient follow-up. Conclusions: ACD is a congenital developmental lesion located in the midline posterior to the anus presenting as a tubular structure without communication with the anal canal, usually discovered in early infancy, and characteristically predominant in girls. The authors recommend that all ACDs, regardness of size and length, should be removed surgically to restore the normal anatomy and to avoid delayed presentation of infection such as perianal abscess or fistula formation. J Pediatr Surg 38:758-762. © 2003 Elsevier Inc. All rights reserved.

We investigated the in vitro effect of trichostatin (histone deacetylase inhibitor) on cell proliferation, cell cycle regulation and apoptosis in renal cell carcinoma cell lines. Trichostatin significantly inhibited the proliferation of all six cell lines examined in dose-dependent manner with IC50 of about 125-250 nM. Trichostatin (72-h incubation) induced a G1 phase arrest in ACHN, Caki-1, Caki-2 and Renca cell lines and a G2-M phase arrest in A498 cells. When we examined the effects of this drug on ACHN cells, trichostatin decreased the levels of CDK4, CDK6, cyclin D1 and cyclin A proteins. p27 protein was increased by trichostatin. In addition, trichostatin markedly enhanced the binding of p27 with CDK2 and CDK4. Furthermore, the activities of CDK2, CDK4- and CDK6-associated kinase were reduced and the lack of the CDK activity was paralleled by increased hypophosphorylation of Rb protein. Trichostatin also induced apoptosis in all the renal cell carcinoma cell lines. Apoptotic process of ACHN cells was associated with the changes of Bcl-2, caspase-9, caspase-3, caspase-7 proteins as well as mitochondria transmembrane potential (deltapsim) loss. Taken together, these results demonstrate that trichostatin inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

Previously, we showed that monensin, Na + ionophore, potently inhibited the growth of acute myelogenous leukemia and lymphoma cells. Here, we demonstrate that monensin inhibited the proliferation of renal cell carcinoma cells with IC 50 of about 2.5 μM. Monensin induced a G 1 or a G 2 -M phase arrest in these cells. When we examined the effects of this drug on ACHN cells, monensin decreased the levels of CDK2, CDK6, cdc2, cyclin A and cyclin B1 proteins. p21 and p27 proteins were increased by monensin. In addition, monensin markedly enhanced the binding of p21 with CDK2 and the binding of p27 with CDK6. Furthermore, the activities of CDK2- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Monensin also induced the apoptosis in several renal cell carcinoma cells. Apoptotic process of Caki-2 cells was associated with the changes of Bcl-2, Bcl- XL , caspase-9, caspase-3, caspase-7 proteins as well as mitochondria transmembrane potential (ΔΨ m ) loss. Taken together, these results demonstrate for the first time that monensin inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

Previously, we showed that monensin, Na+ ionophore, potently inhibited the growth of acute myelogenous leukemia and lymphoma cells. Here, we demonstrate that monensin inhibited the proliferation of solid tumor cells with IC50 of about 2.5 micro M. Monensin induced a G1 or a G2-M phase arrest in these cells. When we examined the effects of this drug on SNU-C1 cells, monensin decreased the levels of CDK2, CDK4, CDK6, cyclin D1 and cyclin A proteins. While p27 was increased by monensin, p21 was not. In addition, monensin markedly enhanced the binding of p27 with CDK2, CDK4 and CDK6. Furthermore, the activities of CDK2-, CDK4- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Monensin also induced apoptosis in solid tumor cells. Apoptotic process of SNU-C1 cells was associated with the changes of Bax, caspase-3 and mitochondria transmembrane potential (deltapsim). Taken together, these results demonstrated for the first time that monensin inhibited the growth of solid tumor cells, especially SNU-C1 cells, via cell cycle arrest and apoptosis.

Ultrasound-guided water enema (USWE) reduction was performed in 115 patients with intussusception, which was diagnosed by ultrasound between April 1988 and August 1992 at Keimyung University Dongsan Medical Center. The overall rate of successful reduction was 80.9%. The rate was 91.0% for patients with symptoms ofor = 24 hours' duration, and 61.1% for patients with symptoms of more than 24 hours' duration (P.001). Six patients had recurrence during the study period (recurrence rate, 5.2%). There was no perforation or other complications during and after the water enema reduction. The authors conclude that (1) USWE reduction for childhood intussusception has a higher rate of successful reduction and a lower rate of recurrence than does barium enema and (2) USWE is safe and may be an alternative method in the nonoperative treatment of intussusception.

Previously, we showed that arsenic trioxide potently inhibited the growth of myeloma cells and head and neck cancer cells. Here, we demonstrate that arsenic trioxide inhibited the proliferation of all the renal cell carcinoma cell lines (ACHN, A498, Caki-2, Cos-7, and Renca) except only one cell line (Caki-1) with IC(50) of about 2.5-10 microM. Arsenic trioxide induced a G(1) or a G(2)-M phase arrest in these cells. When we examined the effects of this drug on A498 cells, arsenic trioxide (2.5 microM) decreased the levels of CDK2, CDK6, cyclin D1, cyclin E, and cyclin A proteins. Although p21 protein was not increased by arsenic trioxide, this drug markedly enhanced the binding of p21 with CDK2. In addition, the activities of CDK2- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Arsenic trioxide (10 microM) also induced apoptosis in A498 cells. Apoptotic process of A498 cells was associated with the changes of Bcl-(XL), caspase-9, caspase-3, and caspase-7 proteins as well as mitochondria transmembrane potential (Deltapsi(m)) loss. Taken together, these results demonstrate that arsenic trioxide inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

Monensin, a Na+ ionophore, regulates many cellular functions, including apoptosis. We investigated the in vitro antiproliferative effect of monensin on nine human lymphoma cell lines. Monensin significantly inhibited the proliferation of all the lymphoma cell lines examined with a 50% inhibition concentration of about 0.5 micromol/l, and induced a G1 and/or a G2-M phase arrest in these cell lines. To address the antiproliferative mechanism of monensin, we examined the effect of this drug on cell-cycle-related proteins in CA46 cells (both G1 and G2 arrest) and Molt-4 cells (G2 arrest). Treatment with monensin for 72 h decreased CDK4 and cyclin A levels in CA46 cells, and cdc2 levels in Molt-4 cells. In monensin-treated CA46 cells, increased p21-CDK2, p27-CDK2 and p27-CDK4 complex forms were observed. And, in monensin-treated Molt-4 cells, increased p21-cdc2 complex form was detected. Furthermore, the activities of CDK2- and CDK4-associated kinases were reduced in association with Rb hypophosphorylation in monensin-treated CA46 cells. The activity of cdc2-associated kinase was decreased in both cell lines, which was accompanied by induction of Wee1. Also, monensin induced apoptosis in these cell lines, as evidenced by annexin V binding assay and flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with loss of mitochondria transmembrane potential (Delta(psi)m). Taken together, these results demonstrated for the first time that monensin potently inhibits the proliferation of human lymphoma cell lines via cell cycle arrest and apoptosis.

A case of congenital immature gastric teratoma along with spontaneous gastric perforation in a 1-day-old boy is presented. The clinical features are similar to those of meconium peritonitis. Coincidentally, the child had an arachnoid cyst at 25 months of age. To the best of the authors knowledge, this case of congenital immature gastric teratoma associated with gastric perforation mimicking meconium peritonitis, is the first description in the English-language literature. J Pediatr Surg 37:E11. Copyright 2002, Elsevier Science (USA). All rights reserved.

Previously, we reported that EB1089 inhibited the growth of NCI-H929 myeloma cells via cell cycle arrest and apoptosis. In the present study, we investigated whether a combined EB1089 and TGF-beta1 synergistically inhibited the cell proliferation of myeloma cell lines. While TGF-beta1 alone could not inhibit the proliferation of any of the tested myeloma cells, synergistic effect between EB1089 (1 x 10(-8) M) and TGF-beta1 (1 ng/ml) was observed in NCI-H929 cells. TGF-beta1 intensified the decreased expression of CDK2, CDK4, CDK6 and cyclin D1 in EB1089-treated NCI-H929 cells. However, these effects did not intensify to decrease CDK2 activity of EB1089-treated NCI-H929 cells, resulting in no difference in the extent of G1 arrest between EB1089- and both agents-treated cells. Remarkably, both agents synergistically induce apoptosis of NCI-H929 cells, which was accompanied with up-regulation of Bax, degradation of PARP and Rb proteins, and loss of mitochondrial transmembrane potential (deltapsim). EB1089 caused the induction of SMAD4, a mediator of TGF-beta1 signaling. In addition, a combined EB1089 and TGF-beta1 increased p21 and JNK/SAPK activity whereas neither EB1089 nor TGF-beta1 affected p21 and JNK/SAPK activity. Taken together, these results suggest that treatment with both EB1089 and TGF-beta1 synergistically inhibits the proliferation of NCI-H929 cells through apoptosis.

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor to have the anti-tumor effect. Here, we evaluated the anti-growth effect of SAHA on lung cancer (A549, SK-LU-1, HCC-95, HCC-1588, NCI-H460, NCI-H1299, Calu-6, HCC-33, NCI-H69) and normal lung (human small airway epithelial cells and human pulmonary fibroblast) cells in relation to reactive oxygen species (ROS) and thioredoxin (Trx) levels. SAHA inhibited the growth of lung cancer cells, and induced a G2/M phase arrest and apoptotic cell death in these cancer cells. In contrast, SAHA did not significantly inhibit the growth of normal lung cells and induce apoptotic cell death. Concerning the oxidative stress, SAHA increased ROS levels in lung cancer cells and induced glutathione (GSH) depletion. Moreover, it decreased the expression level of Trx1 in lung cancer cells. While the overexpression of Trx1 attenuated death and GSH depletion in SAHA-treated lung cancer cells, the downregulation of Trx1 intensified those in these cells. In addition, SAHA increased miR-629 level in lung cancer cells. The mRNA level of Trx1 was decreased by SAHA. Furthermore, the 3′ UTR region of Trx1 was regulated by miR-629. In conclusion, SAHA inhibited the growth of lung cancer cells via cell cycle arrest and apoptosis. The growth inhibition was related to the levels of Trx1 and miR-629. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2008-0062279) and supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, (2013006279). Citation Format: Bo Ra You, Bo Ram Han, Woo Hyun Park. Change in miRNA by suberoylanilide hydroxamic acid affects lung cancer cell death via regulating thioredoxin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2263. doi:10.1158/1538-7445.AM2014-2263

Hepatopulmonary syndrome (HPS) is a serious complication of end-stage liver disease, which is characterized by hypoxia, intrapulmonary vascular dilatation, and liver cirrhosis. Liver transplantation (LT) is the only curative treatment modality for patients with HPS. However, morbidity and mortality after LT, especially in cases of severe HPS, remain high. This case report describes a patient with typical findings of an extracardiac pulmonary arteriovenous shunt on contrast-enhanced transesophageal echocardiography (TEE), and clubbing fingers, who had complete correction of HPS by deceased donor LT. The patient was a 16-year-old female who was born with biliary atresia and underwent porto-enterostomy on the 55th day after birth. She had been suffered from progressive liver failure with dyspnea, clubbing fingers, and cyanosis. Preoperative arterial blood gas analysis revealed severe hypoxia (arterial O2 tension of 54.5 mmHg and O2 saturation of 84.2%). Contrast-enhanced TEE revealed an extracardiac right-to-left shunt, which suggested an intrapulmonary arteriovenous shunt. The patient recovered successfully after LT, not only with respect to physical parameters but also for pychosocial activity, including school performance, during the 30-month follow-up period.

Arsenic trioxide (As 2 O 3 ) has been shown to inhibit the proliferation of hematologic malignant cells. Previously, we reported that As 2 O 3 had an antitumoral effect in head and neck cancer. Here, we investigated the induction of apoptosis and its mechanism in PCI-I head and neck squamous carcinoma cells, after treatment with As 2 O 3 . Treatment with 2 μM of As 2 O 3 caused apoptosis in PCI-I cells following 3 days of exposure, which was detected by the annexin V-PI and DAPI staining methods. The cell death population was markedly increased, being 88% larger than the As 2 O 3 -untreated control cells. To address the mechanism of apoptosis, a Western blot assay was performed, showing that Bax was up-regulated without a change in Bcl-2. Activation of caspase-9 during As 2 O 3 -induced apoptosis was substantiated by monitoring the proteolysis of the caspase-9, which was associated with an increase of Apaf-1 and cytochrome c protein. PCI-1 cells rapidly changed the mitochondria membrane potential (Δψ m ) after addition of As 2 O 3 . Furthermore, activation of caspase-3 was demonstrated by monitoring the proteolysis of the caspase-3 and by measuring caspase-3 activity with a fluorogenic substrate, which was associated with the cleavage of poly(ADP-ribose) polymerase. To examine the in vivo effect of As 2 O 3 , C3H mouse inoculated with syngenic SCC7 cells was treated by intratumoral injection of As 2 O 3 (300 μg) every day, demonstrating that tumor mass was dramatically reduced on day 4, and revealed induction of apoptosis by TUNEL assay. These results suggest that apoptosis of PCI-1 cells by As 2 O 3 is induced by activation of caspase-3 via cytochrome c, caspase-9 and Apaf-I complex.

Progression of cell cycle in eukaryotes is regulated by a series of the cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs). It has been shown that 1,25(OH)2D3 is able to arrest cell cycle at G1 phase in malignant cells including HL-60 cells. EB1089 is a novel 1,25(OH)2D3 analog that has more potent antileukemic properties with reduced hypercalcemic effect in vitro and in vivo than 1,25(OH)2D3. In the present study, we examined the effect of EB1089 on HL-60 cells at the protein levels of several G1 regulatory proteins. Exposure of HL-60 cells to EB1089 (1x10-8 M) for 3 days showed the G1 block by FACS analysis. The level of p21 was markedly induced in HL-60 cells treated with EB1089 at 24 h, and p27 were progressively increased in a time-dependent manner. The expressions of CDK2 and CDK6 were down-regulated during G1 block of HL-60 cells, and CDK4 is progressively elevated. In addition, level of cyclin D1 was increased in a time-dependent manner, however, no change of cyclin E was noted through the G1 to S traverse. Immunoprecipitation study demonstrated that p27 did not bind to CDK2, CDK4 and CDK6 in EB1089-treated HL-60 cell extracts. In contrast, complexes immunoprecipitated from EB1089-treated HL-60 cells with antibodies CDK2 and CDK6 contained higher amounts of immunodetectable p21 protein compared to untreated HL-60 cells, whereas no detectable change was noted with anti-CDK4 antibody. Furthermore, the kinase activities of CDK2 and CDK6 were decreased while little change was observed in CDK4 activity. These data indicated that p21 protein is a strong candidate for the control of G1 progression in EB1089-treated HL-60 cells, and its major target molecules are CDK2 and CDK6.

EB1089, a 1,25-dihydroxyvitamin D(3) analog, has been known to have potent antiproliferative properties in a variety of malignant cells in vitro and in vivo. In the present study, we analyzed the effect of EB1089 on human myeloma cell lines. EB1089 inhibited the proliferation of NCI-H929 cells and RPMI8226 cells in a dose-dependent manner among three myeloma cell lines tested. The antiproliferative effect of EB1089 on myeloma cells was related to the expression level of vitamin D receptor. To investigate the mechanism of the antiproliferative effect of EB1089, cell cycle analysis was attempted in EB1089-sensitive NCI-H929 cells. EB1089 (1 x 10(-8) M) efficiently induced G(1) arrest of the cell cycle. Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089. In addition, EB1089 (1 x 10(-8) M, 72 h) increased the protein level of the CDKI p27 and markedly enhanced the binding of p27 with CDK2 compared to EB1089-untreated cells. Furthermore, the activity of CDK2-associated cyclin kinase was decreased, which was accompanied by the reduction of cyclin-D1-, cyclin-E-, and cyclin-A-associated kinase activities, resulting in the hypophosphorylation of Rb protein. These results suggest that EB1089 can inhibit the proliferation of human myeloma cells, especially NCI-H929 cells, via a G(1) block in association with the induction of p27 and the reduction of CDK2 activity.

Androgens are postulated to act indirectly on the gubernaculum via the genitofemoral nerve, which contains specific neuropeptide transmitters. We examined gubernacula in vitro and in vivo to see if these neuropeptides affected the gubernacular development directly. Gubernacula (n = 272) from male rats (aged 0 to 3 days) were incubated in organ culture with various different neurotransmitters. The cultures were examined daily with a dissecting microscope connected to a video camera and tape. Some rats were anaesthetized and the inguinoscrotal skin was excised to expose the gubernacula for in vivo video recording. Of 181 gubernacula treated with calcitonin gene-related peptide (CGRP) at concentrations of 7 to 714 nmol/L, 92 showed rhythmic contractions. The number of responsive gubernacula was proportional to CGRP concentrations ( r = .685). This compared with 9 of 40 gubernacula treated with vasoactive intestinal peptide and 2 of 25 controls. Neither female gubernacula, skeletal muscle, nor umbilical cord showed CGRP-induced contractions. Gubernacula in vivo showed vigorous contractility and serpentine movements, which were accentuated by increased intraabdominal pressure. These studies demonstrate the gubernaculum to be highly motile during testicular descent. Rhythmic contractions suggest the presence of possible smooth muscle-like components that may be modulated by CGRP release from the genitofemoral nerve.

The reaction of benzal bromides with Co (1 atm) in a binary system (aq. KOH/C 6 H 6 ) in the presence of a catalytic amount of Co 2 (CO) 8 together with benzyltriethylammonium chloride as a phase transfer catalyst for 8 h at room temperature gives the corresponding carboxylic acids in good to excellent yields.

Pyrogallol (PG) is a polyphenol compound and is known to be an O2*- generator. We evaluated the effects of PG on the growth of human gastric cancer SNU-484 cells in relation to the cell cycle and apoptosis. Dose-dependent inhibition of cell growth was observed in SNU-484 cells with an IC50 of approximately 50 microM following treatment with PG for 72 h. DNA flow cytometric analysis indicated that treatment with PG generally did not induce the specific cell cycle phase arrest. Treatment with 50 microM PG induced apoptosis approximately 20%, as evidenced by sub-G1 cells and annexin V-staining cells. Treatment with PG also induced the loss of mitochondrial membrane potential (Delta psi m) in SNU-484 cells. The intracellular reactive oxygen species (ROS) levels including O2*- were significantly increased in PG-treated cells. Furthermore, the depletion of the intracellular glutathione (GSH) content was observed in cells treated with 50 or 80 microM PG. In conclusion, PG inhibited the growth of human gastric cancer SNU-484 cells by inducing cell cycle arrest as well as triggering apoptosis. The changes in ROS and GSH by PG were closely related to apoptosis in SNU-484 cells.

Background/Purpose: The authors evaluated prospectively the utility of ultrasonography, Tc-99m-DISIDA hepatobiliary scintigraphy, and liver needle biopsy in differentiating biliary atresia (BA) from intrahepatic cholestasis in 73 consecutive infants who had cholestasis. Methods: Sixty three ultrasonographic examinations of 61 infants with 7.0-MHz transducer were carried out, focusing on the fibrous tissue at the porta hepatis. The authors defined the triangular cord (TC) as visualization of a triangular or tubular shaped echogenic density just cranial to the portal vein bifurcation on a transverse or longitudinal scan. Results: Although 17 of 20 ultrasonographic examinations from infants who had BA denoted TC, 43 ultrasonographic examinations from infants with either neonatal hepatitis (NH) or other causes of cholestasis denoted no TC, showing a diagnostic accuracy of 95% with 85% sensitivity and 100% specificity. Investigation with Tc-99m-DISIDA hepatobiliary scintigraphy showed that 24 of 25 infants who had BA had no gut excretion, and 16 of 46 infants who had either NH or other causes of cholestasis had gut excretion, showing a diagnostic accuracy of 56% with 96% sensitivity and 35% specificity. Therefore, gut excretion of tracer excluded BA, but no gut excretion of tracer needed further investigations as liver needle biopsy. Forty-four liver needle biopsies were carried out in 19 infants who had BA and 24 infants who had either NH or other causes of cholestasis. Although 18 of 20 biopsy findings in infants who had BA were correctly interpreted as having BA, 23 of 24 biopsy results in infants who had either NH or other causes of cholestasis were correctly diagnosed, showing a diagnostic accuracy of 93% with 90% sensitivity and 96% specificity. Conclusions: Since the introduction of ultrasonographic TC sign in the diagnosis of BA by our institution, we have found that it seemed to be a simple, time-saving, highly reliable, and non-invasive tool in the diagnosis of BA from other causes of cholestasis. The authors propose a new diagnostic strategy in the evaluation of infantile cholestasis with emphasis on ultrasonographic TC sign as first priority of investigations. When the TC is visualized, prompt exploratory laparotomy is mandatory without further investigations. When the TC is not visualized, hepatobiliary scintigraphy is the next step. Excretion of tracer into the small bowel actually rules out BA. Liver needle biopsy is reserved only for the infants with no excretion of tracer. The authors believe that a correct decision regarding the need for surgery can be made in almost all cases with infantile cholestasis by this multidisciplinary approach.

The complication of protruding preperitoneal fat (PPF) is very rare even though PPF is frequently encountered during hernia surgery. It is called a cord lipoma in the surgical literature. Herein, we report a case of a hemorrhagic complication of PPF causing swelling and discomfort in the groin. By preoperative ultrasonography, this was misidentified as an incarcerated inguinal hernia containing omental fat. CASE REPORT

An isolated tubular intestinal loop (ITIL) means an anatomical or vascular communication with rest of the bowel loop and may provide an insight into the pathogenesis of intestinal atresia. We experienced a case of an ITIL identified in omentum of a 4-day-old neonate with type-II intestinal atresia. To our knowledge, this association has never been reported in the English literature. Omental wrapping of the incompletely resorbed ischemic bowel segment may explain this phenomenon in a case of congenital intestinal atresia.

Eleven cases of biliary atresia (BA) and eight of neonatal hepatitis (NH) were studied, using transmission electron microscopy, to document their different ultrastructural characteristics and to elucidate the possible pathogenesis of biliary atresia. Among 30 consecutive liver biopsies obtained from 19 infants with BA or NH, 21 specimens composed (13 BA, 8 NH) were examined ultrastructurally. The electron microscopic features of NH (patients' age range, 35 to 60 days) were (1) giant hepatocytic transformation with scattered areas of dilated endoplasmic reticulum, indicative of intracytoplasmic degeneration, (2) frequent cytoplasmic biliary necrosis, and (3) relatively intact microvilli in most bile canaliculi, which contained some hepatocytic cytoplasmic fragments. These features strongly suggest that the main pathological process in NH is hepatocellular injury rather than bile duct damage. In contrast, all cases with BA (age range, 27 to 130 days) demonstrated (1) marked hepatocellular cholestasis associated with many lysosomes and myelin figures, (2) marked loss of bile canalicular microvilli, (3) degenerated bile ductular cells containing bile pigments, and (4) periductal inflammatory fibrosis. These features suggest that the main pathological process in BA involves the biliary system. A few viral inclusions were observed in two cases with BA, whic suggests that viral infection is a potential cause. In two BA cases (aged 40 and 43 days at the time of first biopsy), the ultrastructural findings essentially were the same as those of NH, and follow-up biopsy specimens (at 48 and 94 days) showed findings consistent with BA. Such results support Landing's hypothesis that BA and NH are different manifestations of a single pathological process.

Chylous ascites is a rare disorder with variables causes. Herein, the authors report a case of refractory chylous ascites after Kasai operation for biliary atresia, which was treated successfully with subcutaneous octreotide, a synthetic somatostatin analogue. To the best of the authors' knowledge, this is the first report in the English-language literature of post-Kasai chylous ascites being successfully treated with subcutaneous octreotide in parallel with the continuation of enteral feeding.

Preduodenal portal vein is a rare congenital anomaly that causes high intestinal obstruction. The authors report on a newborn who was diagnosed as having duodenal obstruction at 30 weeks' gestation. During surgery the patient was found to have duodenal obstruction caused by a preduodenal portal vein. Malrotation was an associated finding. Treatment consisted of Ladd's procedure and a diamond-shaped duodenoduodenostomy performed anterior to the portal vein.

A 2-day-old premature infant with a duodenal duplication cyst situated between the two blind ends of a duodenal atresia is presented. This entity has not been reported previously in the literature. This rare association of a duplication cyst and atresia may occur when recanalization is interrupted, with failure to form a single duodenal lumen.

J Korean Assoc Oral Maxillofac Surg 2012;38:71-7) Objectives: This study sought to investigate the positioning of the posterior superior alveolar artery in relation to the performance of the maxillary sinus bone graft procedure in a Korean population. Materials and Methods: We identified the position of the posterior superior alveolar artery relative to 93 maxillary sinuses in 58 patients and determined the distance from the inferior border of the artery in the premolar and molar areas to the alveolar ridge and sinus floor. Results: The mean distance from the alveolar ridge to the posterior superior alveolar artery in the dentate group (20.62±3.05 mm in the premolar region, 17.50±2.84 mm in the molar region) was greater than as compared to the edentulous group (18.83±2.79 mm in the premolar region, 15.50±1.64 mm in the molar region), and this difference was statistically significant ( P 0.05) between the mean distance from the sinus floor to the posterior superior alveolar artery in the dentate group (8.21±2.79 mm in the premolar region, 7.52±2.07 mm in the molar region) or in the edentulous group (7.75±3.31 mm in the premolar region, 7.97±2.31 mm in the molar region). Conclusion: Prior to surgery, it is important to evaluate the position of the posterior superior maxillary artery by using computed tomography scans. The premolar area is safer than the molar area for performing the maxillary sinus bone graft without bleeding.

Antimycin A (AMA) inhibits the mitochondrial electron transport between cytochromes b and c. However, the relationship between AMA and lung cancer cells is poorly understood. In this study, we investigated the involvement of reactive oxygen species (ROS) and glutathione (GSH) in AMA-treated lung cancer Calu-6 cell death. Treatment with AMA reduced cell viability in a dose-dependent manner for 72 h. The intracellular ROS levels were decreased in Calu-6 cells treated with low doses of AMA (10, 25 or 50 microM) at 72 h. However, the levels increased in cells treated with a high dose of 100 microM AMA. Levels of O2.- were significantly increased in AMA-treated cells at 72 h. The increases in ROS levels including O2.- in AMA-treated cells were observed within 10 min. Treatment with AMA reduced the intracellular GSH content. SOD activity was up-regulated in AMA-treated Calu-6 cells at 72 h. However, catalase activity was down-regulated by AMA. Treatment with tiron, a ROS scavenger, reduced the intracellular ROS levels, which were associated with a partial reduction of apoptosis. Treatment with exogenous SOD and catalase significantly inhibited loss of the mitochondrial transmembrane potential (DeltaPsim) in AMA-treated Calu-6 cells. In conclusion, our results suggest that the changes of intracellular ROS and GSH affect apoptosis in AMA-treated Calu-6 cells.

Comparison of Neonatal Gastrointestinal Perforation Due to Necrotizing Enterocolitis and Other Causes

This is a case report of umbilical cord hernia containing vermiform appendix, which was not reduced to the abdominal cavity by fibrous adhesion to the inner surface of the sac. Appendectomy is required to reduce the herniated bowel and to excise the hernia sac. (J Korean Surg Soc 2011;80:161-163)

Purpose: The purpose of this study is to identify the incidence of metachronous contralateral inguinal hernia (MCH) and how early patients visit hospital upon discovering the presence of a lump on the contralateral side after initial hernia repair. Methods: This is a retrospective study of 2,169 patients with inguinal hernia between January 2001 and January 2010 at a single institution. We evaluated the occurrence of MCH among 1,689 consecutive unilateral inguinal hernia (UIH) patients who were treated in our department. We also analyzed and compared the time lag (number of days) between noticing the presence of hernia and hospital visit between UIH and MCH. Results: A total of 102 patients with MCH underwent initial UIH repair during the study period. The incidence of MCH was 6.0% and was slightly higher in males (6.7%) than in females (3.5%). The patients with left inguinal hernia (7.3%) had higher incidence of developing MCH than those with right (5.2%). When we analyzed the patients with MCH, 69.6% of them were under age 5 and 74.6% of MCH occurred within 2 years after initial UIH repair. Seventy-three percent of the patients with MCH, whose time lag was over one month when the first episode of UIH occurred, visited hospital later as MCH occurred. Conclusion: The incidence of MCH within the study period is 6.0%. It is slightly higher in males and in patients with left inguinal hernia. Most MCH occurred under age 5 and within 2 years after initial UIH repair.

The suthors present the case of 4-month-old girl with a midline prepubic sinus extending from the skin overlying the pubis to the superior surface of the bladder, and continuing to the umbilicus via the median umbilical ligament. The distal portion of the exicised sinus was surrounded by concentric bundles of collagen and smooth muscle with minimal inflammatory infiltrates, which suggests a developmental origin. According to Stephens' classification, the sinus appears to be a variant of dorsal urethral duplication of Stephens type 3.

This is an analysis of 6 patients with enteric duplications seen over an 8 year period at the Department of Pediatric Surgery, Dongsan Medical Center. They were all males but one. All duplications were cystic, and single except one. Locations of duplications were in the duodenum in one patient, in the jejunum in one, and in the terminal ileum in four. Five of the 6 patients were seen within 1 year of life. Three were newborn infants who had symptoms of intestinal obstruction with palpable mass since birth. Duplication cyst acted as a leading point of intussusception in 4 month and 8 month old infants respectively. One jejunal duplication was found in an 11-year-old boy who had malrotation of the midgut with Ladd's bands. Clinical presentation, embryogenesis of duplication, and management are discussed.

Purpose: Long-term survival of biliary atresia patients after Kasai’s portoenterostomy is being increasingly reported. Although extended survival has been achieved for many patients, factors influencing outcome have not been defined clearly. The authors investigated 5-year survival rates and prognostic factors for survival after Kasai’s portoenterostomy using univariate and multivariable methods. Methods: The authors analyzed 5-year survival rates and prognostic factors in 56 patients who underwent Kasai’s portoenterostomy during the period from 1991 to 2005 by the Kaplan-Meier model and Cox proportional hazards model, respectively. Both clinical factors and histological features of the liver and periportal fibrous mass were analyzed as prognostic factors. Results: Younger ages of less than 90 days at surgery, clearance of jaundice and absence of post-Kasai cholangitis in 6 months were predictive of a favorable outcome. A significant difference between the live and the dead was found with regard to an average of 7 or more bile ductules in periportal fibrous mass in 200 HPF (P=0.013). The external diameter of the longest bile ductule in the periportal fibrous mass is not correlated to the prognosis (P=0.49). Independent factors for good prognosis were jaundice-free in 6 months and over 7 bile ductules density in periportal fibrous mass. Conclusion: Favorable outcome after Kasai’s portoenterostomy for biliary atresia is determined by bilirubin clearance in 6 months after Kasai operation and seven or more bile ductules in periportal fibrous mass. The 5-year post-Kasai survival rate is 77.2%.