A two decade survey of respiratory adenovirus in Taiwan: the reemergence of adenovirus types 7 and 4

From November 1999 to December 2001, three outbreaks of adenovirus (Ad) respiratory infection occurred in southern Taiwan. To determine the circulating serotypes and molecular epidemiology, a total of 524 virus strains were randomly selected from 1,064 strains isolated from 1981 to 2001, and were studied using restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR)-RFLP. The major subgenus found was subgenus B (45%), followed by subgenus E (29%) and subgenus C (25%). Ad3 and Ad7 were the major types found during the 1st outbreak, which occurred from November 1999 to March 2000, while Ad4 was found mainly during the 2nd and 3rd outbreaks in October 2000 and September 2001, respectively. Both Ad7 and Ad4 were reemerged serotypes, whereas Ad3 was consistently isolated during the survey, although it declined drastically from 36 to 2% in 2001. Genotype analysis in this study showed that the only strain of Ad7 found in 1983 was Ad7a, but all randomly selected strains of Ad7 isolated during 1999-2000 were Ad7b. The clinical features of 217 patients were analyzed during the 1999-2000 outbreaks. About 79% of the total cases were less than 7 years old. The ratio of male to female was 2:1. Severe infections, such as pneumonia and acute bronchitis, accounted for nearly half of the cases (43%). These results show the reemergence and changing of serotypes, the clinical association of respiratory adenovirus infections, and the molecular epidemiology of Ad7 genotypes in Taiwan during the past two decades.     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.     

Autonomic dysregulation as a basis of cardiovascular, endocrine, and inflammatory disturbances associated with obstructive sleep apnea and other conditions of chronic hypoxia, hypercapnia, and acidosis

Obstructive sleep apnea has traditionally been viewed as a structural disease. A multitude of systemic endocrine and cardiovascular abnormalities have been previously attributed to the prevalence of obesity in these patients. A growing body of clinical evidence, however, points to a relationship between sleep apnea and its systemic abnormalities independent of obesity. We hypothesize that this association is based on a maladaptive autonomic response of chemoreceptors, reacting to the hypoxia, hypercapnia, and acidosis of sleep apnea. The elevated sympathetic response triggers an inflammatory cascade that results in a myriad of downstream consequences including insulin resistance, hypertension, diabetes, atherosclerosis and metabolic syndrome. The sympathetic bias and endocrine disturbances may further exacerbate sleep disturbance in a potentially pernicious cycle. Our proposal may extend to any chronic respiratory or metabolic conditions that manifest hypoxia, hypercapnia, and acidosis and elicit a maladaptive autonomic and inflammatory response.     

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.     

Effects of x-ray and CT image enhancements on the robustness and accuracy of a rigid 3D/2D image registration

A rigid body three-dimensional/two-dimensional (3D/2D) registration method has been implemented using mutual information, gradient ascent, and 3D texturemap-based digitally reconstructed radiographs. Nine combinations of commonly used x-ray and computed tomography (CT) image enhancement methods, including window leveling, histogram equalization, and adaptive histogram equalization, were examined to assess their effects on accuracy and robustness of the registration method. From a set of experiments using an anthropomorphic chest phantom, we were able to draw several conclusions. First, the CT and x-ray preprocessing combination with the widest attraction range was the one that linearly stretched the histograms onto the entire display range on both CT and x-ray images. The average attraction ranges of this combination were 71.3 mm and 61.3 deg in the translation and rotation dimensions, respectively, and the average errors were 0.12 deg and 0.47 mm. Second, the combination of the CT image with tissue and bone information and the x-ray images with adaptive histogram equalization also showed subvoxel accuracy, especially the best in the translation dimensions. However, its attraction ranges were the smallest among the examined combinations (on average 36 mm and 19 deg). Last the bone-only information on the CT image did not show convergency property to the correct registration.     

Fine-needle aspiration cytology of sarcomatoid renal cell carcinoma: A morphologic and immunocytochemical study of 15 cases

Sarcomatoid renal cell carcinoma (SRCC), which accounts for 5% of all renal cell carcinomas (RCC), has a worse prognosis than conventional nonsarcomatoid RCC. making accurate diagnosis important. This study reports on the morphologic and immunocytochemical features of 15 cases of SRCC (9 primary tumors and 6 metastases) diagnosed by fine-needle aspiration (FNA) biopsy. All but three cases showed a dimorphic cell population consisting of varying proportions of a high-grade epithelial component, either clear or granular-cell type and a spindle cell (sarcomatoid) component, of either fibrosarcomatous, malignant fibrous histiocytoma (MFH), or unclassified types. The sarcomatoid component in the biphasic and monophasic tumors stained positively for cytokeratin in 12 of 14 (85%) cases, for vimentin in 10 of 11 (91 %) cases, and for muscle-specific action in 4 of 11 (36%) cases. Of note, the three cases that demonstrated a purely sarcomatoid morphology stained positively for cytokeratin. Unlike in studies performed on surgically resected specimens, neither the proportion of the sarcomatoid component nor the presence of necrosis had prognostic significance, the discrepancy most likely being related to the sampling. We conclude that SRCC, both primary and metastatic, can be accurately diagnosed by FNA when cytologic features are evaluated in conjunction with immunocytochemical findings.     

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.     

Mutational analysis of Fas ligand gene in human non-Hodgkin lymphoma

Among the systems triggering apoptosis, the Fas-Fas ligand (FasL) system is recognized as a major pathway for the induction of apoptosis in cells and tissues. Ligation of Fas by either an agonistic antibody or FasL transmits a 'death signal' to the target cell, potentially triggering apoptosis. Alterations of genes along the Fas-mediated apoptosis pathway have been reported in many human cancers. However, there have been no data regarding FasL gene mutations in human cancers. We hypothesized that FasL gene mutation might be involved in the development of non-Hodgkin lymphoma (NHL). In this study, we analyzed the entire coding region of the FasL gene for the detection of somatic mutations in a series of 111 NHLs and found that one tumor had a FasL gene mutation in the cytoplasmic domain. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant in 293T cells, but couldn't find any significant loss of cell death compared to the wild-type FasL. Together, these data suggest that FasL is occasionally mutated in human NHL and that FasL mutations appear to play no role in the pathogenesis of the vast majority of NHLs.