mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency.

Transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). Transition from cirrhosis to hepatocarcinogenesis depends on mitochondrial oxidative stress, as controlled by cytosolic aldose metabolism through the pentose phosphate pathway (PPP). Progression to HCC is critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Although AR inactivation blocked susceptibility to hepatocarcinogenesis, it enhanced growth restriction, carbon trapping in the non-oxidative branch of the PPP and failed to reverse the depletion of glucose 6-phosphate (G6P) and liver cirrhosis. Here, we show that inactivation of the TAL-AR axis results in metabolic stress characterized by reduced mitophagy, enhanced overall autophagy, activation of the mechanistic target of rapamycin (mTOR), diminished glycosylation and secretion of paraoxonase 1 (PON1), production of antiphospholipid autoantibodies (aPL), loss of CD161+ NK cells, and expansion of CD38+ Ito cells, which are responsive to treatment with rapamycin in vivo. The present study thus identifies glycosylation and secretion of PON1 and aPL production as mTOR-dependent regulatory checkpoints of autoimmunity underlying liver cirrhosis in TAL deficiency.

Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis.

Oxidative stress modulates carcinogenesis in the liver; however, direct evidence for metabolic control of oxidative stress during pathogenesis, particularly, of progression from cirrhosis to hepatocellular carcinoma (HCC), has been lacking. Deficiency of transaldolase (TAL), a rate-limiting enzyme of the non-oxidative branch of the pentose phosphate pathway (PPP), restricts growth and predisposes to cirrhosis and HCC in mice and humans. Here, we show that mitochondrial oxidative stress and progression from cirrhosis to HCC and acetaminophen-induced liver necrosis are critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Both TAL and AR are confined to the cytosol; however, their inactivation distorts mitochondrial redox homeostasis in opposite directions. The results suggest that AR acts as a rheostat of carbon recycling and NADPH output of the PPP with broad implications for disease progression from cirrhosis to HCC.

Learning curve in robotic transabdominal preperitoneal (rTAPP) ventral hernia repair: a cumulative sum (CUSUM) analysis.

PURPOSE: rTAPP-VHR is a novel technique which may be added to a surgeon's armamentarium. We aim to evaluate the robotic transabdominal preperitoneal ventral hernia repair (rTAPP-VHR) learning curve based on operative times while accounting for peritoneal flap integrity. METHODS: We performed a retrospective analysis of a database collected over a 7-year period. Patients with primary ventral hernias were included and a cumulative sum analysis(CUSUM) was used to create learning curves for three subsets of operative times. A risk-adjusted CUSUM (RA-CUSUM) accounted for repair quality based on peritoneal flap completeness. The flap was considered as incomplete when peritoneal gaps were unable to be closed. RESULTS: 105 patients undergoing rTAPP-VHR were included. Learning curves were created for skin-to-skin, console, and off-console times. Patients were divided into three phases. In terms of skin-to-skin times, both phase 2&3 had a mean 11 min shorter than that of phase 1 (p = 0.0498, p = 0.0245, respectively), with a steady decrease after forty-six cases. An incomplete peritoneal flap was noted in 25/36 patients in phase 1, as compared to 5/24 and 5/45 patients in phase 2&3, respectively. When risk-adjusted for peritoneal flap completeness, gradually decreasing skin-to-skin times were observed after sixty-one cases. In terms of off-console times, the mean across three phases was 14 min, with marked improvement after forty-three cases. CONCLUSIONS: Forty-six cases were needed to achieve steadily decreasing operative times. We can assume that ensuring good-quality repairs, through maintenance of peritoneal flap integrity, was gradually improved after sixty-one cases. Moreover, familiarization with port placements and robotic docking was accomplished after forty-three cases.

Extended approach or usage of nasoseptal flap is a risk factor for olfactory dysfunction after endoscopic anterior skullbase surgery: results from 928 patients in a single tertiary center.

BACKGROUND: The aim of this study was to compare olfactory function change in patients who underwent endoscopic skull-base surgery. METHODOLOGY: A total of 928 patients were included in this retrospective study. Olfactory function was measured using the non- validated Likert scale (0â€"100), the Cross-Cultural Smell Identification Test (CC-SIT) and the butanol threshold test (BTT). Patients were divided into two groups: an endoscopic trans-sellar approach group (ETA, n = 768) and an extended endoscopic endonasal approach group (EEEA, n = 160). The ETA group was sub-divided into Nasoseptal flap (NSF) and no NSF groups. RESULTS: Non-validated olfactory function significantly worsened in the EEEA and ETA-NSF groups compared with that in the ETA- no NSF group for at least 6 months post-operatively. Validated olfactory impairment (BTT and CC-SIT) was also significantly worse in the EEEA and NSF groups compared with that in the ETA-no NSF group 3 months post-operatively. Additionally, the degrees of non-validated and validated olfactory deterioration were not significantly different between the EEEA and ETA-NSF groups. We also found that CC-SIT score changes were significantly impaired in tuberculum sellae meningioma patients than in craniopharyn- gioma patients. CONCLUSIONS: We conclude that NSF was the key factor that led to olfactory impairment after endoscopic skull-base surgery.

Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac.

Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1(-/-)) or Epac2 (Epac2(-/-)) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2(-/-) mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2(-/-) mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2(-/-) mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis.

The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis.

Mounting evidence suggests reconceptualizing osteoarthritis (OA) as an inflammatory disorder. Trauma and obesity, the common risk factors of OA, could trigger the local or systemic inflammatory cytokines cascade. Inflammatory bone loss has been well documented; yet it remains largely unknown about the link between the inflammation and hypertrophic changes of subchondral bone seen in OA, such as osteophytosis and sclerosis. Amid a cohort of inflammatory cytokines, endothelin-1 (ET-1) could stimulate the osteoblast-mediated bone formation in both physiological (postnatal growth of trabecular bone) and pathological conditions (bone metastasis of prostate or breast cancer). Also, ET-1 is known as a mitogen and contributes to fibrosis in various organs, e.g., skin, liver, lung, kidney heart and etc., as a result of inflammatory or metabolic disorders. Subchondral bone sclerosis shared the similarity with fibrosis in terms of the overproduction of collagen type I. We postulated that ET-1 might have a hand in the subchondral bone sclerosis of OA. Meanwhile, ET-1 was also able to stimulate the production of matrix metalloproteinase (MMP)-1 and 13 by articular chondrocytes and synoviocytes, by which it might trigger the enzymatic degradation of articular cartilage. Taken together, ET-1 signaling may play a role in destruction of bone-cartilage unit in the pathogenesis of OA; it warrants further investigations to potentiate ET-1 as a novel diagnostic biomarker and therapeutic target for rescue of OA.

Extraocular muscle injury during endoscopic sinus surgery: a series of 10 cases at a single center.

BACKGROUND: Extraocular muscle (EOM) injury is a rare but serious complication of endoscopic sinus surgery (ESS). The aim of this study is to describe the clinical characteristics and course of EOM injury occurring during ESS. DESIGN: Retrospective case series. METHODS: Medical records and CT images of patients who suffered from EOM injury after ESS between 2006 and 2012 were retrospectively reviewed. Patient demographics, endoscopic anatomy, type of surgery (primary or revision), predisposing risk factors, site and extent of injury on CT imaging, and associated complications were evaluated. In addition, data regarding ophthalmologic management and clinical outcomes were collected. RESULTS: Ten patients with EOM injuries after ESS were included in this study. One patient was undergoing revision ESS. All patients sustained medial rectus muscle injury and one patient suffered concurrent ipsilateral inferior rectus muscle injury. A microdebrider was used in nine cases. Right-sided injury (90% of patients) was more prevalent than left-sided injury, and 70% of injured medial rectus muscles were completely transected. After subsequent strabismus surgery, 8/9 patients regained binocular single vision in primary gaze despite residual diplopia in some gaze positions. CONCLUSION: Although proper ophthalmologic surgery after EOM injury may improve deviation in the primary gaze position, none of the patients regained normal EOM movement. Therefore, prevention of this complication through adequate surgical technique and precautions is important.

Evaluation of inferior turbinate outfracture outcomes using computed tomography.

BACKGROUND: Outfracture of the inferior turbinate (IT) presents numerous advantages, but it is generally believed that the lateralized IT will resume its original position. The purpose of this study was to evaluate the outcome of IT outfracture objectively using computed tomography (CT). METHODOLOGY: Fifteen patients who underwent bilateral IT outfracture for the removal of pituitary adenomas by the endonasal approach were enrolled. The angles between the lateral wall of the nasal cavity (NC) and IT on both sides were measured from CT scans before and at least 6 months after operation. In addition, we evaluated the effects of variables including age, thickness of IT attachment site and width of the nasal floor, on the angles. RESULTS: Regardless of the side where a Hardy retractor was placed, the angle between the lateral wall of the NC and IT decreased significantly within 6 months after the outfracture compared to preoperative values on both sides. Other variables showed no significant correlations with the angle between the IT and the lateral wall of the NC. CONCLUSION: The outfracture procedure effectively lateralized the IT and it maintained that position for at least 6 months after the operation.

The value of dual-time-point 18F-FDG PET/CT for identifying axillary lymph node metastasis in breast cancer patients.

OBJECTIVE: The sensitivity of 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for detecting axillary lymph node (ALN) metastases in breast cancer is reported to be low. Several studies have shown, however, that dual-time-point (18)F-FDG PET imaging provides improved accuracy in the diagnosis of certain primary tumours when compared with single-scan imaging. The purpose of this study was to assess whether the use of dual-time-point (18)F-FDG PET/CT scans could improve the diagnostic accuracy of ALN metastasis in breast cancer. METHOD: The study included 171 breast cancer patients who underwent pre-operative (18)F-FDG PET/CT scans at 2 time-points, the first at 1 h after radiotracer injection and the second 3 h after injection. Where (18)F-FDG uptake was in the ALN perceptibly increased, the maximum standardised uptake values for both time-points (SUVmax1 and SUVmax2) and the retention index (RI) were calculated. Correlation between the PET/CT results and post-operative histological results was assessed. RESULTS: The performance of 1 h and 3 h PET/CT scans was equal, with sensitivity 60.3% and specificity 84.7%, in detecting ALN metastasis. Out of 171 patients, 60 had ALNs with increased (18)F-FDG uptake on 1 h or 3 h images. There was no significant difference in RI between the metastatic ALN-positive group and the node-negative group. The area under the receiver operating characteristic (ROC) curve for SUVmax1 was 0.90 (p<0.001) and 0.87 for SUVmax2 (p<0.001). CONCLUSION: Dual time-point imaging did not improve the overall performance of (18)F-FDG PET/CT in detecting ALN metastasis in breast cancer patients.

Significance of incidental focal uptake in prostate on 18-fluoro-2-deoxyglucose positron emission tomography CT images.

To evaluate the clinical significance of incidental focal prostate fluorodeoxyglucose (FDG) uptake, we reviewed 18-F-FDG positron emission tomography (PET)/CT scans from 2003 to 2007 and selected cases with focal FDG uptake in prostate. Cases of known prostate cancer were excluded. The maximum standardised uptake value (SUV(max)), site (central or peripheral) and pattern (discrete or ill-defined) of FDG uptake, calcification (present or absent) and prostate volume (<30 or ≥30 cc) were recorded. The PET/CT findings were correlated with serum prostate-specific antigen (PSA) levels, imaging studies, clinical follow-up and biopsy. Of a total of 5119 cases, 63 (1.2%) demonstrated focal FDG uptake in prostate. Eight cases were lost to follow-up. Among the 55 cases with follow-up, malignancy was confirmed by biopsy in 3 (5.4%). The three malignant cases had SUV(max) values of 3.3, 3.6 and 2.3, and all were noted in the peripheral portion of prostate; two of these cases had a discrete FDG uptake pattern, none had calcification corresponding to the FDG uptake area and one had a prostatic volume greater than 30 cc. The mean SUV(max) of 52 benign cases was 3.2 ± 1.7 and focal FDG uptake was noted in the peripheral portion in 34 (65%), 20 (38%) cases showed a discrete FDG uptake pattern, 35 (67%) were accompanied by calcification and 32 (62%) had a prostatic volume greater than 30 cc. The majority of cases demonstrating focal FDG uptake in prostate were benign and no PET/CT finding could reliably differentiate benign from malignant lesions; however, when discrete focal FDG uptake without coincidental calcification is seen, particularly in the peripheral zone of the prostate, further clinical evaluation is recommended.

Posthumous diagnosis of long QT syndrome from neonatal screening cards.

BACKGROUND: Molecular autopsy in sudden unexplained death in the young (SUDY) victims cannot usually be performed if tissue suitable for DNA extraction is not retained at autopsy. OBJECTIVE: The purpose of this study was to assess the feasibility and clinical value of posthumous genetic testing for long QT syndrome (LQTS) using residual material from the neonatal screening (Guthrie) card in SUDY victims. METHODS: Twenty-one cases were investigated up to 13 years after death. Deaths occurred at <1 year in one, 1-18 years in 18, and 19-35 years in two patients. Guthrie cards were 3-39 years old. DNA was extracted, and amplicons corresponding to the coding regions of the LQTS genes 1, 2, 3, 5, and 6 underwent either denaturing high-performance liquid chromatography screening or direct DNA sequencing. RESULTS: Adequate DNA was extracted in every case, although repeated purification and amplification was often required. Rare variants were detected in six of 19 cases undergoing diagnostic screening. Four (21%) are considered to be pathological and have been used for family screening: R243C and H455Y in KCNQ1 in 12-year-old and 13-year-old boys, respectively, and Q81H and S621R in KCNH2 in 21-month and 28-year-old females, respectively. Variants of uncertain significance were R1047L in KCNH2 in a 2-year-old girl and S38G in KCNE1 in a 19-month-old boy. Point mutation tests for previously identified familial LQTS mutations revealed a positive result in both cases: E146K in KCNQ1 and exon 6-4del in KCNH2. CONCLUSION: Residual material from Guthrie cards collected for newborn metabolic screening can be used as a reliable source of DNA for the posthumous diagnosis of LQTS decades after SUDY, although purification and amplification of DNA is time intensive.

Sinonasal inverted papilloma: value of convoluted cerebriform pattern on MR imaging.

BACKGROUND AND PURPOSE: A convoluted cerebriform pattern (CCP) has been reported as a valuable MR imaging feature of inverted papilloma (IP). The purpose of this study was to validate the usefulness of CCP for distinguishing IP from various malignant sinonasal tumors in a relatively large number of patients. MATERIALS AND METHODS: We retrospectively reviewed MR images of 30 patients with IP and 128 patients with various malignant sinonasal tumors proved on histologic examination and compared the prevalence of a CCP between the 2 groups. In 8 patients with IP concomitant with squamous cell carcinoma, we also tried to find the MR features to help suggest coexistent malignancy. RESULTS: A CCP was demonstrated in all 30 (100%) of the IPs and 17 (13%) of the 128 malignant sinonasal tumors on MR imaging. There was a significant statistical difference in the prevalence of a CCP between IP and malignant sinonasal tumors with the overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy 100%, 87%, 64%, 100%, and 89%, respectively. Of 8 IPs concomitant with squamous cell carcinoma, a focal loss of a CCP was demonstrated in 4 tumors, 3 of which also showed aggressive bone destruction with extrasinonasal extension on MR images. CONCLUSION: Although a CCP is a reliable MR imaging feature of sinonasal IPs, it can also be seen in various malignant sinonasal tumors. A focal loss of a CCP might be a clue to the diagnosis of IPs concomitant with malignancy.

Comparison of surgical conditions during propofol or sevoflurane anaesthesia for endoscopic sinus surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is often affected by intra-nasal bleeding, which can be influenced by various anaesthetics and preoperative conditions. This study compared the surgical condition and the amount of intra-nasal bleeding between patients given sevoflurane/remifentanil (SR) and propofol/remifentanil (PR) anaesthesia. METHODS: ASA I or II patients undergoing ESS were randomly assigned to group SR (n=20) or group PR (n=20). The extent of the preoperative surgical lesion was classified as high (> 12) and low Lund-Mackay (LM) (< or = 12) scores according to the computed tomography findings. The amount of intraoperative blood loss was calculated from the patients' haemoglobin (Hb) and the amount of blood in the suction canister. The surgeons rated the visibility of the surgical field on a numeric rating scale (NRS). RESULTS: In the high-LM score patients, the median (1st/3rd quartiles) blood loss for the SR and PR groups was 135 (121/222) and 19 (8/71) ml h(-1), respectively (P<0.01), and the mean (SD) of NRS was 5.8 (2.3) and 2.3 (1.0), respectively (P<0.05). However, in patients with low-LM score, both blood loss and NRS scores were not different between groups SR and PR. CONCLUSIONS: In the high-LM score patients, PR anaesthesia results in less blood loss and a better surgical conditions for ESS than SR anaesthesia.

Focal hyperostosis on CT of sinonasal inverted papilloma as a predictor of tumor origin.

BACKGROUND AND PURPOSE: To evaluate the CT characteristics of focal hyperostosis in patients with sinonasal inverted papilloma and to correlate these characteristics with the detection of the origins of tumors. MATERIALS AND METHODS: Paranasal sinus and nasal cavity CT images of 76 patients were reviewed retrospectively to detect areas within which there was focal hyperostosis. We correlated the sites on the CT scans within which there was focal hyperostosis with the origin of the tumors described in the corresponding patient's medical records. We also evaluated the CT features of focal hyperostosis according to the origin of tumors. RESULT: Surgical evaluation of 55 lesions with focal hyperostosis in CT images revealed that 49 of these lesions coincided with the actual origin of tumor. The CT-based determination of the locations of the areas of focal hyperostosis corresponded to the actual tumor origin in 89.1% of cases. Especially in cases with focal hyperostosis within the frontal, maxillary, sphenoid, and posterior ethmoid sinuses, areas of focal hyperostosis corresponded to the origin of tumor without exception. In the evaluation of the CT features of focal hyperostosis, 2 patterns of localized bone thickening were noted. Plaquelike bone thickening was seen mainly when focal hyperostosis involved the lateral wall of the nasal cavity. On the other hand, cone-shaped bone thickening was seen only in the walls of the paranasal sinuses or the bony septum. CONCLUSIONS: A high correlation between the origin of the inverted papilloma and focal hyperostosis on CT might facilitate preoperative prediction of tumor origin by radiologists and rhinologists.

Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses.

XIAP-associated factor 1 (XAF1) is a new candidate tumor suppressor, which has been known to exert proapoptotic effects by interfering with the caspase-inhibiting activity of XIAP. To explore the XAF1's candidacy for a suppressor in urogenital tumorigenesis, we investigated the XAF1 status in a series of cancer cell lines and primary tumors derived from the bladder, kidney and prostate. Expression of XAF1 transcript was undetectable or extremely low in 60% (3/5) of bladder, 66% (10/15) of kidney, and 100% (3/3) prostate cancer cell lines. Abnormal reduction of XAF1 was also found in 33% (18/55) of primary bladder and 40% (8/20) of primary kidney tumors, and showed a correlation with advanced stage and high grade of bladder tumor. Hypermethylation at 14 CpG sites in the 5' proximal region of the XAF1 promoter was highly prevalent in cancers versus adjacent normal or benign tissues and tightly associated with reduced gene expression. XAF1 expression enhanced the apoptotic response of tumor cells to chemotherapeutic agents, such as etoposide or 5-FU. While XAF1 expression did not influence the subcellular distribution or expression of XIAP, it elevated the protein stability of p53 and its target gene expression. Moreover, the apoptosis-sensitizing and growth suppression function of XAF1 was markedly impeded by blockade of p53 function. Collectively, our study demonstrates that epigenetic alteration of XAF1 is frequent in human urogenital cancers and may contribute to the malignant progression of tumors by rendering tumor cells a survival advantage partially through the attenuated p53 response to apoptotic stresses.

An improved method for determination of ethyl carbamate in Korean traditional rice wine.

An improved extraction method for ethyl carbamate, a genotoxic and carcinogenic compound found in various fermented foods and beverages, was investigated for its determination in the two most typical Korean traditional rice wines, takju and yakju. When the rice wines were extracted twice with chloroform at 30 degrees C for 60 min, the recovery of ethyl carbamate was less than 16%. When they were saturated with NaCl before extraction, the recovery of ethyl carbamate increased to 24.4% in takju and 67.2% in yakju. Adjustment of pH to 9.0 after NaCl saturation in takju resulted in a dramatic increase of recovery to 81.2%, but not in yakju. When the contents of ethyl carbamate and its precursor, urea, in various Korean traditional rice wines were determined, there was no correlation between the two contents. This is due to the fact that storage time is more important than urea content in the formation of ethyl carbamate in rice wine. In addition, its storage at high temperature resulted in a dramatic increase in ethyl carbamate content according to the prolonged storage time, suggesting that storage time and temperature play a key role in the formation of ethyl carbamate in Korean traditional rice wine.

Corneal opacity after repeated photorefractive keratectomy.

Corneal opacity developed in an eye that had photorefractive keratectomy (PRK) with a 193 nm excimer laser 5 times over 3 years. Six months after the last PRK, a partial penetrating keratoplasty was performed. The cornea was stained and immunohistochemically evaluated for collagen types. Light microscopy showed thickening of epithelial layers, proliferation of subepithelial fibroblasts, and the absence of Bowman's membrane. Transmission electron microscopy showed irregular collagen lamellae and electron-dense deposits adjacent to keratocytes. The staining was positive for Alcian blue, and immunohistochemistry was positive for type IV and VI collagen. This case suggests that corneal opacity after repeated PRK is the result of deposits of type IV and VI collagen and acidic mucoprotein in the extracellular matrix.

Hydrogen peroxide is a novel inducer of connective tissue growth factor.

Connective tissue growth factor (CTGF) has recently been described as a fibrogenic factor and is greatly induced by various extracellular stimuli, such as transforming growth factor-beta (TGF-beta), dexamethasone, and serotonin. CTGF induces collagen type I and fibronectin, and the deposition of such molecules leads to fibrotic disease in many tissues. Intracellular reactive oxygen species (ROS) are generated by extracellular stress conditions and are produced as by-products of cellular metabolism. Imbalanced cellular redox status is a potent pathogenic factor that leads to various degenerative diseases, including tissue fibrosis. Since CTGF is believed to play a crucial role in fibrotic disease formation in many tissues, we examined the role of ROS in CTGF gene expression in human lens epithelial cell line B3. The results showed that CTGF was induced by reactive oxygen species such as hydrogen peroxide and hydroxyl radicals. Next, we examined whether CTGF induction by ROS is via newly synthesized TGF-beta. The results showed that ROS directly induced CTGF mRNA not via the increased TGF-beta synthesis or activation. Next, we treated AG490, which is the well-known inhibitor of Janus kinase (JAK), with hydrogen peroxide. AG490 abrogated the CTGF induction by ROS in a dose-dependent manner. The results suggest that JAK-2/-3 seems to be involved in the enhanced CTGF mRNA expression by hydrogen peroxide. In this report, we present that hydrogen peroxide is a novel inducer of CTGF gene expression and that JAK-2/-3 activation seems to play a role in CTGF induction.

Is the re-closure of surgically induced open neural tube defect the repetition of primary neurulation? An experimental study with chick embryos.

It is well known that surgically induced open neural tube defects (ONTDs) tend to re-close in early embryonic stages. To investigate whether the process of re-closure is a repetition of primary neurulation, the morphological changes of surgically induced ONTDs were chronologically examined in early chick embryos. Longitudinal incisions of 3-somite length were made in the neural tubes of chick embryos at Hamburger and Hamilton stage 18 or 19. About half of the embryos showed complete closure of the skin on surgical microscopic examination. The re-closed neural tubes showed no remarkable differences from the controls on histological examination. The process of re-closure involved a zipper-like (ventral to dorsal) closure in the transverse sections of neural tubes. The results indicate that the re-closure of surgically induced ONTDs does not repeat the process of natural primary neurulation.

Computed tomography anatomy of the anterior ethmoid canal.

The roof of the anterior ethmoid swings up anteriorly from its more or less horizontal course at the point where the anterior ethmoid canal (AEC) is situated. The AEC is an important structure in endoscopic sinus surgery since its injury results in bleeding into the nasal cavity and may result in intraorbital bleeding. We therefore investigated the location of this canal and the anatomic characteristics of the area surrounding the canal using coronal computed tomography (CT) of the paranasal sinuses. One hundred sides of 50 paranasal coronal CT images in patients with sinusitis were analyzed to assess the location of the AEC, the shape of the superolateral wall of the ethmoid sinus anterior and posterior to the AEC, and pneumatization of the roof of the anterior ethmoid sinus. The AEC is situated in the second quarter of the roof of the ethmoid sinus. The superolateral wall anterior to the AEC demonstrated an acute angle in 99% of sides, while the superolateral wall posterior to the AEC showed an obtuse angle in 87% of sides. The ethmoid cell anterior to the AEC pneumatized posteriorly over the AEC in 26% of sides. We conclude that coronal CT confirmation of the anatomic characteristics of the AEC, and the area surrounding the canal, is invaluable for preoperative planning for endoscopic sinus surgery.