Biliary atresia with associated complicated anorectal and urogenital malformations

We report on a girl with biliary atresia (BA) who also suffered with anorectal agenesis without fistula and complicated urogenital malformation. The outcome of patients with these severe anomalies is poor, but she has survived without liver and/or renal transplantation for more than 3 years. A careful treatment plan for each anomaly in addition to prevention of cholangitis and urinary tract infection is indispensable for managing these complicated anomalies.     

Activation of invasiveness of cervical carcinoma cells by angiotensin II

OBJECTIVE: Angiotensin II recently has been reported to promote the growth of several kinds of cells. In this study, we investigated the effect of angiotensin II on cervical carcinoma cells. STUDY DESIGN: The expression of angiotensin II type I receptor was examined by immunohistochemistry in normal and neoplastic cervical tissues. Invasion assay was examined in Siha cells (cervical squamous cell carcinoma) and vascular endothelial growth factor levels were assayed with a vascular endothelial growth factor enzyme-linked immunosorbent assay kit. RESULTS: Mean staining intensity level was stronger in invasive carcinoma cells than in normal, dysplasia, and carcinoma in situ tissues. Angiotensin II induced the secretion of vascular endothelial growth factor from Siha cells. Furthermore, angiotensin II promoted the invasive potential of Siha cells. These effects were reversed by the addition of anti-human vascular endothelial growth factor antibody and candesartan (antagonist of angiotensin II type I receptor). CONCLUSION: Angiotensin II is involved in the progression of cervical carcinoma, because it induces the secretion of vascular endothelial growth factor through angiotensin II type I receptor, which results in the increased invasiveness of carcinoma cells.     

Automated computerized scheme for detection of unruptured intracranial aneurysms in three-dimensional magnetic resonance angiography

RATIONALE AND OBJECTIVES: A computerized scheme for automated detection of unruptured intracranial aneurysms in magnetic resonance angiography was developed based on the use of a three-dimensional selective enhancement filter for dots (aneurysms). MATERIALS AND METHODS: Twenty-nine cases with 36 unruptured aneurysms (diameter, 3 to 26 mm; mean, 6.6 mm) and 31 non-aneurysm cases were used in this study. The isotropic 3-dimensional magnetic resonance angiography images with 400 x 400 x 128 voxels (voxel size, 0.5 mm) were processed by use of the selective enhancement filter. The initial candidates were identified by use of a multiple gray-level thresholding technique on the dot-enhanced images and a region-growing technique with monitoring some image features. All candidates were classified into four types of candidates according to the size and local structures based on the effective diameter and skeleton image of each candidate (ie, large candidates and three types of small candidates including short-branch type, single-vessel type, and bifurcation type). In each group, a number of false-positives were removed by use of different rules on localized image features related to gray levels and morphology. Linear discriminant analysis was used for further removal of false-positives. RESULTS: With this computer-aided diagnostic scheme, all of 36 aneurysms were correctly detected with 2.4 false-positives per patient based on a leave-one-out-by-patient test method. CONCLUSION: This computer-aided diagnostic system would be useful in assisting radiologists for the detection of intracranial aneurysms in magnetic resonance angiography.     

Surgery without skin resection for eyelid entropion

The previously reported surgical methods for eyelid entropion are basically manipulations of the skin or the conjunctival surface. When entropion is marked, manipulations also involve the tarsus. In the most widely used method, the eyelashes are directed outward by horizontal wedge resection of an appropriate amount of the excessive skin in the ciliary vestibule. This method is simple and effective but sometimes causes recurrences, conspicuous scars due to tension of the resection site, or lagophthalmos due to excessive resection. We speculated that partial swelling of the orbicularis muscle at the front of the tarsus is one of the main causes of pediatric eyelid entropion and found that correction of entropion is possible by partial resection of this muscle without skin resection. Eight patients with congenital entropion were treated by this method, and good results were obtained.     

Application of an artificial neural network to high-resolution CT: usefulness in differential diagnosis of diffuse lung disease

OBJECTIVE: The purpose of our study was to evaluate the diagnostic performance of an artificial neural network (ANN) in differentiating among certain diffuse lung diseases using high-resolution CT (HRCT) and the effect of ANN output on radiologists' diagnostic performance. MATERIALS AND METHODS: We selected 130 clinical cases of diffuse lung disease. We used a single three-layer, feed-forward ANN with a back-propagation algorithm. The ANN was designed to differentiate among 11 diffuse lung diseases by using 10 clinical parameters and 23 HRCT features. Therefore, the ANN consisted of 33 input units and 11 output units. Subjective ratings for 23 HRCT features were provided independently by eight radiologists. All clinical cases were used for training and testing of the ANN by implementing a round-robin technique. In the observer test, a subset of 45 cases was selected from the database of 130 cases. HRCT images were viewed by eight radiologists first without and then with ANN output. The radiologists' performance was evaluated with receiver operating characteristic (ROC) analysis with a continuous rating scale. RESULTS: The average area under the ROC curve for ANN performance obtained with all clinical parameters and HRCT features was 0.956. The diagnostic performance of four chest radiologists and four general radiologists was increased from 0.986 to 0.992 (p = 0.071) and 0.958 and 0.971 (p < 0.001), respectively, when they used the ANN output based on their own feature ratings. CONCLUSION: The ANN can provide a useful output as a second opinion to improve general radiologists' diagnostic performance in the differential diagnosis of certain diffuse lung diseases using HRCT.     

Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cells by overexpression of AP-2alpha

A previous report demonstrated that AP-2alpha favors the survival of ovarian cancer patients by clinical findings. However, the functional roles of AP-2alpha in human ovarian cancers have not been determined. To clarify the roles, we overexpressed AP-2alpha in SKOV3 human ovarian cancer cells, which originally possess little AP-2alpha. AP-2alpha overexpression changed cell morphology from spindle to epithelioid type and suppressed cell proliferation and invasion, which would be partially correlated with decreased phosphorylation levels of the erbB2, Akt and ERK pathways, increased E-cadherin and reduced pro-matrix metalloproteinase-2 levels. Moreover, nude mice intraperitoneally injected with AP-2alpha-overexpressing cells survived longer than those with neo-transfected cells. The present data represent the first direct evidence that AP-2alpha plays a tumor suppressive role in ovarian cancer.     

A message for young child neurologists: a lesson from the Nobel Prize centennial

The Nobel Prize was created in 1901, according to the will of Alfred Nobel who left tremendous estate by inventing of dynamite. In the fields of natural science, prizes are given to distinguished scientists in three categories, namely physics, chemistry, and physiology or medicine. During the past 100 years, the Nobel Prize have become undoubtedly the most prestigious international prize. Nobel laureates are always the most respected scientists in the world. There have been 478 recipients in the three categories, 177 of them belonging to physiology or medicine. In March 2002, an international forum commemorating the centennial of the Nobel Prize was held in Tokyo and Kyoto under the auspices of the Science Council of Japan, focusing upon creativity. Guest speakers including prize winners, officers of the Nobel Foundation, and members of the Nobel Committee participated actively. In particular, Japanese laureates, including Drs. Ezaki, Tonegawa, Shirakawa and Noyori met together at the Symposium, and discussed what is creativity and how it is nurtured? At about the same time the Centennial Exhibition of the Nobel Prize was held in the National Science Museum in Tokyo. From these two commemorative events, informative messages were extracted and given to young colleagues of the Japanese Society of Child Neurology.     

Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disorders (LPD) of children and young adults are sometimes termed as severe chronic active EBV infection (CAEBV), and are associated with an aggressive clinical course. However, these clinicopathological states and the role of EBV have not been clarified. A retrospective study was performed on 43 children and adult patients, who manifested EBV-associated T/NK-cell lymphoproliferative disorders (EBV-T/NK-LPD) and most of whom had experienced general illness with CAEBV for several months or years. Clinicopathologically, 43 patients were classified into four groups: group A (smoldering state) (n=7), morphological non-neoplastic LPD with chronic clinical course (several years); group B (chronic state) (n=10), non-neoplastic LPD with clonal EBV-infected cells and a chronic course; group C (leukemia/lymphoma state) (n=22), neoplastic LPD with a subacute course (years to months); group D (fulminant state) (n=4), neoplastic LPD with a fulminant course (weeks to days). The 43 patients comprised 21 males and 22 females. The median age of group A was 14 years, group B 12 years, group C 17 years, and group D 1 year. Four of 7 patients in group A, 3 of 10 in group B, 12 of 22 in group C, and all 4 in group D have died. Causes of death included hemophagocytic syndrome and/or tumor death. Genotypically and phenotypically, group C was composed of peripheral T-cell lymphoma (PTCL), and NK-cell leukemia/lymphoma (NKLL), and group D comprised cases of PTCL. Groups A and B exhibited increased NK- or T-cells (CD8>CD4), and rare B-cells. Serologic titers of EBV were only modestly elevated or not elevated in almost all cases. EBV early RNA-1 (EBER-1)-expressing EBV-infected cells were frequently encountered in each group, but the number of infected cells varied between the cases. The EBV genotype did not differ between the groups. Our findings support an important pathogenic role for EBV-infected T/NK-cell infection, rather than the EBV state, in CAEBV and consequent EBV-associated NK/T-neoplasia.     

Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta

AIMS: Membrane-bound aminopeptidases in human placenta are thought to be involved in maintaining homeostasis during pregnancy by metabolizing bioactive peptides such as oxytocin and angiotensin at the interface between the fetus and mother. Because determining the precise localization of these enzymes is required to support this notion, we investigated the ultrastructural localization of two principal enzymes, aminopeptidase A (APA; EC 3.4.11.7)/angiotensinase and placental leucine aminopeptidase (P-LAP; EC 3.4.11.3)/oxytocinase in human first trimester and full-term placenta. METHODS: Immunohistochemical analysis using anti-P-LAP and anti-APA antibodies was performed on ultrathin frozen sections of fixed human placental villi. RESULTS: Transmission immunoelectron microscopy revealed that both enzymes were expressed on the surface of apical microvilli of syncytiotrophoblast cells and, to a lesser extent, on the basal infoldings. The location of the two enzymes did not vary between the first trimester and full-term placenta sections, while the staining intensities were slightly enhanced in full-term villi. CONCLUSIONS: Our observation that P-LAP and APA are present on the microvilli, which is a site of interaction between the mother and fetus, suggests possible involvement of these enzymes in cleaving peptide hormones from the fetus and mother in order to regulate bioactivity.     

Levels of placenta growth factor in gestational trophoblastic diseases

OBJECTIVE: The aim of the current study was to investigate levels of placenta growth factor in the tissues and sera of the patients with gestational trophoblastic disease and to determine its usefulness for the treatment of gestational trophoblastic disease. STUDY DESIGN: Placenta growth factor concentrations were measured in the tissue homogenates of 12 normal placentas, 33 complete hydatidiform moles, and 6 gestational choriocarcinomas. Serum placenta growth factor levels were determined in 59 women with normal pregnant course, in 30 women with complete hydatidiform mole, in 36 women with persistent gestational trophoblastic disease, and 100 nonpregnant healthy volunteers. RESULTS: Serum and tissue placenta growth factor levels in the patients with mole tended to be decreased compared with the levels in normal pregnancy; the levels were increased significantly in patients with choriocarcinoma. When serum placenta growth factor levels were >20 pg/mL (normal upper limit in nonpregnant women), placenta growth factor-to-human chorionic gonadotropin ratios were increased significantly in patients with persistent gestational trophoblastic disease. CONCLUSION: Serum placenta growth factor levels are not of any predictive value in patients with hydatidiform mole. However, elevated serum placenta growth factor levels with increased placenta growth factor-to-human chorionic gonadotropin ratios are suggestive of persistent gestational trophoblastic disease.