Magnesium Exchanged Zirconium Metal-Organic Frameworks with Improved Detoxification Properties of Nerve Agents.

UiO-66, MOF-808 and NU-1000 metal-organic frameworks exhibit a differentiated reactivity toward [Mg(OMe)2(MeOH)2]4 related to their pore accessibility. Microporous UiO-66 remains unchanged while mesoporous MOF-808 and hierarchical micro/mesoporous NU-1000 materials yield doped systems containing exposed MgZr5O2(OH)6 clusters in the mesoporous cavities. This modification is responsible for a remarkable enhancement of the catalytic activity toward the hydrolytic degradation of P-F and P-S bonds of toxic nerve agents, at room temperature, in unbuffered aqueous solutions.

Influence of hepatic dysfunction on the pharmacokinetics and safety of fimasartan.

This study was designed to assess the pharmacokinetics (PK) and safety of fimasartan, an angiotensin II type 1 receptor blocker, in hepatic impairment patients as compared with healthy subjects. An open-label, single-dose, parallel study was conducted in 6 healthy male volunteers and 12 subjects with hepatic impairment. Healthy subjects were matched with hepatic dysfunction patients on the basis of age, gender, and body weight. After a single 120-mg oral administration of fimasartan, PK parameters and safety were analyzed between the hepatic dysfunction groups and healthy group. Compared with the healthy subjects, the geometric mean ratio and 90% confidence intervals for the maximum plasma concentration and the mean area under the plasma concentration-time curve from 0 to infinity (AUC)inf were 0.77 (0.24-2.47) and 1.11 (0.50-2.46), respectively, for the mild hepatic impairment and 6.55 (3.56-12.03) and 5.17 (4.19-6.37), respectively, for moderate hepatic impairment. However, there was no significant difference in time to peak plasma concentration (t(max)) and elimination half-life, and there were no serious or severe adverse events in all subjects. Subjects with mild hepatic impairment exhibited similar bioavailability compared with healthy subjects, whereas subjects with moderate hepatic impairment seemed to exhibit a higher level of systemic exposure to fimasartan than healthy subjects. In addition, all subjects were tolerable with fimasartan.

Study on evaporation characteristics of a sessile drop of sulfur mustard on glass.

The evaporation characteristics (evaporation rates and process) of a sessile drop of sulfur mustard on glass has been studied using a laboratory-sized wind tunnel, gas chromatograph mass spectrometry, and drop shape analysis. It showed that the evaporation rates of the droplet increased with temperature and air flow. The effect of temperature on the rates was more pronounced at lower air flow. Air flow was less effective at lower temperature. The contact angle of the droplet was initially observed as θ = 19.5° ± 0.7 and decreased linearly with time until it switched to a constant mode.

Expression of bone morphogenic protein-4 is inversely related to prevalence of lymph node metastasis in gastric adenocarcinoma.

PURPOSE: Bone morphogenic proteins (BMPs) are the largest subfamily of the transforming growth factor-ß superfamily. Initially characterized as factors that induce bone and cartilage formation, BMPs have been found to be critical during mesoderm formation, organogenesis, and cellular differentiation. Bone morphogenic proteins are also known to modulate the morphologic alteration, adhesion, motility, and invasion of carcinoma cells derived from several organs. However, BMP-4 expression in gastric adenocarcinoma has not yet been clarified. We conducted the present study to define the clinical significance of BMP-4 expression in gastric carcinoma. METHODS: Using immunohistochemistry, we investigated the expression of BMP-4 in normal mucosae and gastric adenocarcinoma samples from 64 patients with gastric carcinoma. RESULTS: The expression of BMP-4 was significantly higher in the adenocarcinoma than in the normal mucosae. Moreover, increased BMP-4 expression was associated with the presence of Helicobacter pylori infection. By contrast, the BMP-4 expression rate in gastric carcinoma was inversely related to the prevalence of lymph node metastasis and tumor invasiveness. CONCLUSIONS: The findings of this study suggest that BMP-4 expression may be a useful prognostic factor for predicting the outcome of patients with gastric carcinoma. Continued investigation to define the pathophysiologic mechanism underlying the role of BMP-4 in gastric carcinoma is warranted.

Distal appendiceal dilatation in equivocal appendicitis may be a useful sign for prediction of normal appendix.

Despite many efforts to reduce unnecessary appendectomy for appendicitis, the negative appendectomy rate remains relatively high. Here, we investigated predisposing factors for normal appendix by analyzing the surgical outcomes for patients with equivocal appendicitis. Over a 3-year period, 1516 patients underwent treatment for appendicitis and 148 (10%) were prospectively diagnosed with equivocal appendicitis. We defined equivocal appendicitis as a right lower quadrant pain with tenderness and an apppendiceal diameter of 6 to 9 mm without appendicolith or severe adjacent inflammation as radiological findings. We investigated normal appendix rates in relation to clinical and radiological features. Of the 148 patients, 48 (32%) had a normal appendix and 100 had appendicitis. A higher normal appendix rate was found for low white blood cell count than for leukocytosis (41% vs 23%, odds ratio (OR) = 2.48), and laparoscopic treatment was then open (42% vs 21%, OR = 2.58). Distal appendiceal dilatation, as determined by radiological imaging, was associated with a higher normal appendix rate than whole dilatation (60% vs 27%, OR = 3.96). Low white blood cell count, laparoscopic treatment, and distal appendiceal dilatation were significant predisposing factors for normal appendix after surgery. Radiologically determined distal dilatation of the appendix may be a useful sign for predicting normal appendix.

Unique design of superior metal-organic framework for removal of toxic chemicals in humid environment via direct functionalization of the metal nodes.

Unique chemical and thermal stabilities of a zirconium-based metal-organic framework (MOF) and its functionalized analogues play a key role to efficiently remove chemical warfare agents (ex., cyanogen chloride, CNCl) and simulant (dimethyl methylphosphonate, DMMP) as well as industrial toxic gas, ammonia (NH3). Herein, we for the first time demonstrate outstanding performance of MOF-808 for removal of toxic chemicals in humid environment via special design of functionalization of hydroxo species bridging Zr-nodes using a triethylenediamine (TEDA) to form ionic frameworks by gas phase acid-base reactions. In situ experimental analyses and first-principles density functional theory calculations unveil underlying mechanism on the selective deposition of TEDA on the Zr-bridging hydroxo sites (µ3-OH) in Zr-MOFs. The crystal structure of TEDA-grafted MOF-808 was confirmed using synchrotron X-ray powder diffraction (SXRPD). Furthermore, operando FT-IR spectra elucidate why the TEDA-grafted MOF-808 shows by far superior sorption efficiency to other MOF varieties. This work provides design principles and applications how to optimize MOFs for the preparation for versatile adsorbents using diamine grafting chemistry, which is also potentially applicable to various catalysis.

A polyhedral oligomeric silsesquioxane functionalized copper trimesate.

A metal-organic framework (MOF), copper trimesate (Cu3(BTC)2), was selectively functionalized with aminopropylisooctyl polyhedral oligomeric silsesquioxane (O-POSS) to make the external surface of Cu3(BTC)2 hydrophobic and thereby enhance the stability of the material against humidity. POSS modification was also successfully applied to other MOFs such as MOF-74 and MIL-100.

Laparoscopic total extraperitoneal repair of lumbar hernia.

Lumbar hernia is a rare surgical entity without a standard method of repair. With advancements in laparoscopic techniques, successful lumbar herniorrhaphy can be achieved by the creation of a completely extraperitoneal working space and secure fixation of a wide posterior mesh. We present a total extraperitoneal laparoendoscopic repair of lumbar hernia, which allowed for minimal invasiveness while providing excellent anatomical identification, easy mobilization of contents and wide secure mesh fixation. A total extraperitoneal method of lumbar hernia repair by laparoscopic approach is feasible and may be an ideal option.

Prognostic significance of HLA class I expressing in gastric carcinoma defined by monoclonal anti-pan HLA class I antibody, EMR8-5.

INTRODUCTION: Downregulation or loss of HLA class I molecules has been demonstrated in human cancers. The aim of this study was to assess the clinical significance of HLA class I expression in gastric cancer. METHODS: Gastric cancer tissues from 189 patients were examined for expression of HLA class I heavy chain antigens by immunohistochemical staining with EMR8-5. The expression level of HLA class I of tumor cells is categorized by combining an estimate the percentage of immunoreactive cell with an estimate of the staining intensity. The relationship between HLA class I expression and clinicopathologic parameters, patient survival, and tumor recurrence were analyzed. RESULTS: HLA class I was downregulated in 85 (45.0%) of the gastric carcinomas. Staining revealed 104 (55.0%) tumors with strongly positive expression of HLA class I antigens, 76 (40.2%) tumors with weakly positive expression, and 9 (4.8%) tumors with negative expression. The expression of HLA class I antigen did not correlate with any other clinicopathologic parameters. Moreover, HLA class I expression was neither a risk factor for tumor recurrence nor survival. CONCLUSION: The downregulation of HLA class I expression is not associated with patient prognosis.

Predictable factors for lymph node metastasis in early gastric cancer-analysis of single institutional experience.

INTRODUCTION: Prediction of lymph node metastasis in early gastric cancer (EGC) is very important to decide treatment strategies preoperatively. The aim of this study was to evaluate factors that predict the presence of lymph node metastasis and to identify the differences between mucosal and submucosal gastric cancers. METHODS: A total of 376 patients with EGC who underwent gastrectomy from March 1999 through December 2007 were retrospectively identified. The clinopathological factors and biological markers (p53, Ki67) were analyzed. RESULTS: The rate of lymph node metastasis was 9.6% (mucosal cancer 2.8%, submucosal cancer 18.4%). Tumor size, depth of invasion, macroscopic type, and lymphovascular invasion were related to lymph node metastasis in EGC. When the carcinomas were confined to the mucosal layer, tumor size and lymphovascular invasion showed significant correlation with lymph node metastasis. On the other side, macroscopic type and lymphovascular invasion were association with lymph node metastasis in submucosal carcinoma. CONCLUSION: The risk factors for lymph node metastasis in EGC are quite different depending on depth of tumor invasion. To predict lymph node metastasis in EGC, it is recommended that distinct assessment according to individual situation should be clearly established.

Association of the human leukocyte antigen class II alleles with chronic atrophic gastritis and gastric carcinoma in Koreans.

OBJECTIVE: Gastric carcinogenesis is a multi-step process and is influenced by several etiological agents, including the host's genetic factors. Since whether a patient remains with chronic superficial gastritis (CSG) or progresses to either chronic atrophic gastritis (CAG) or gastric carcinoma (GC) could be a genetic predisposition unique in each population, we hypothesized that host human leukocyte antigen (HLA) alleles could be discriminative in predicting the risk of CSG progression to precancerous CAG and GC in Koreans. METHODS: A total of 165 patients with gastric disorders (CSG, 62; CAG, 69 and GC, 34), were selected to investigate the association of HLA class II alleles with the progression of CSG to CAG or GC. HLA genotypes were obtained by the polymerase chain reaction-sequence based typing method. RESULTS: The phenotypic frequencies of DRB1*1101 and DQA1*0505 were significantly higher in the CAG group compared to those in the CSG group. In the subjects with Helicobacter pylori (H. pypori) (+), the frequencies of DRB1*1501 and DQB1*0602 were significantly lower in the CAG compared to those in the CSG. Further analysis showed that sex (P < 0.05, OR = 0.41-0.42) and age (P < 0.05, OR = 1.05) also affected the risk of progression from CSG to CAG in H. pylori (+) patients carrying the DRB1*1501 or DQB1*0602 allele. Additionally, the frequency of DRB1*0404 in the GC group was significantly higher than that in the gastritis group. CONCLUSION: Our findings strongly imply an association between HLA class II alleles and the risk of CAG development and GC progression in Koreans.

Phase I/II trial with docetaxel and S-1 for patients with advanced or recurrent gastric cancer with consideration to age.

PURPOSE: To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer. PATIENTS AND METHODS: Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1-14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60-75 mg/m(2) and S-1 60-80 mg/m(2). A phase II study was conducted with the recommended dose (RD) based on phase I. RESULTS: Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m(2) and S-1 60 mg/m(2). Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m(2) and S-1 80 mg/m(2)) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35-66%) and median survival was 15.3 months (95% CI, 10.0-20.6 months). CONCLUSIONS: Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities.

Expression of MUC2 in gastric carcinomas and background mucosae.

BACKGROUND AND AIM: Gastric carcinomas contain elements of both intestinal and diffuse types. Such heterogeneous components may distort the evaluation of the role of the mucin MUC2 in gastric carcinoma. The role of MUC2 expression in background mucosa is not yet clarified. METHODS: We analyzed the expression of MUC2 in gastric mucosa and intestinal metaplasia adjacent to the tumoral area and carcinomas (n = 98) using immunohistochemistry. The immunoreactivity was quantified using an immunohistochemical scoring system. RESULTS: In the intestinal metaplasia adjacent to the tumoral area, MUC2 was detected in 76 (97.4%) of 78 intestinal metaplasia, and MUC2 expression was inversely associated with the depth of wall penetration (P = 0.026) and tumor stage (P = 0.021). Although the expression rate of MUC2 antigens was higher in intestinal-type adenocarcinoma than in diffuse-type adenocarcinoma, a significant correlation with pathologic staging of the TNM system (pTNM staging) and MUC2 expression could not be found in each subtype of gastric carcinomas. CONCLUSION: The expression of MUC2 in intestinal metaplasia was higher in tumors of earlier stages. These findings suggest that increased MUC2 expression in intestinal metaplasia in the neighborhood of the carcinomas may play an important role in gastric carcinomas. Further investigations regarding the role of MUC2 expression in gastric carcinoma and background mucosae are necessary.

Laparoscopic assisted distal rectal cancer resection with preoperative concurrent chemoradiotherapy.

PURPOSE: Anatomy of deep pelvis, narrow distal margin and tumor invasion into neighbor organ are obstacles for curative radical resection for advanced cancer of distal rectum. Technically, laparoscopic application after downstaging the tumor with preoperative concurrent chemotherapy (CCRT) may give a solution to overcome the anatomical difficulties. We compared the results of laparoscopic surgery in the patients who received CCRT with those of patients who had conventional surgery. MATERIALS AND METHODS: A continuous infusion of 5FU plus leucovorin and radiotherapy (50.4 Gy) in 28 fractions was given each patient as CCRT. They underwent D2 radical resection with TME and ANP for the rectal cancer in 4 weeks. RESULTS: Thirty three patients had laparoscopic resection such as LAR, colo-anal anastomosis and APR. The results were compared with 12 cases of the conventional resections. As a result of preoperative CCRT, the cancer was down-staged in 71%. Two year disease free survival was 75% and 74% in the group of conventional and laparoscopic resection, respectively (p=0.427). Ileus, voiding difficulty and leakage after surgery were not different between two groups. Weakness of ejaculation was noted in 9 approximately 11% of both groups. The DFS of the preoperative CCRT followed by radical resection in the groups with a response was more favorable than that in the group with progressive or stable disease. CONCLUSION: Radical resection of advanced distal rectal cancer could be done with performing a laparoscopic assisted operation after CCRT induced down-staging. We may suggest that laparoscopic assisted resection is a good treatment option as it doesn't increase the complications and it has a compatible survival rate to conventional surgery.

A clinicopathologic study of glomus tumor of the stomach.

Glomus tumors are benign lesions and originate from modified smooth muscle cells of the glomus body. These tumors are commonly observed in the dermis or subcutis, but only rarely found in the stomach. Here we report a case of a 67-year-old patient in whom glomus tumor of the stomach was diagnosed after 10-day history of melena. We have reviewed the 13 cases selected from literature of gastric glomus tumor in Korean, including our case. The age of onset ranged from 30 to 68 years (median 54 y) with a strong female dominance (10 females and 3 males). The tumors typically presented with gastrointestinal bleeding or ulcerlike symptom, and 6 tumors had mucosal ulceration. The tumor sizes varied from 1.2 to 3.8 cm (median 2.5 cm), and all tumors presented in antrum of stomach. Microscopically, the tumors were well-circumscribed, and composed of uniform, small, round to polygonal cells. Mitotic activity was usually low. The characteristics of gastric glomus tumors in Korean patients are very similar to those of Western populations. Although gastric glomus tumors can be considered more likely benign, a small possibility of malignant behavior cannot be ruled out.

Multiple symmetric lipomatosis: Korean experience.

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disorder that is characterized by abnormal adipose tissue growth mainly at the neck, abdominal wall, back, shoulder girdle, and arms. A suggested mechanism for accumulation of adipose tissue is a defect in the lipolytic pathway of fat cell. OBJECTIVE: To evaluate the clinical, morphologic, and biochemical findings in Korean patients. METHOD: A total of 32 patients with MSL were evaluated retrospectively. Ten patients were seen at our hospital. The remaining 22 patients from literature were reviewed. Biochemical analyses and neurologic studies were performed. RESULTS: All cases were a sporadic form of MSL. The age of onset ranged from 26 to 70 years (mean of 49.4 years). The male-to-female ratio was 31:1. All but two patients were alcoholics with a daily intake of more than 80 g of alcohol for at least 10 years. In metabolic studies of 17 patients, a Fredrickson type IIb or IV hyperlipoproteinemia was found in three patients. High-density lipoprotein cholesterol values were higher in three patients. A glucose tolerance test was abnormal in five patients. A high prevalence of neurologic abnormalities was observed. Clinical signs of peripheral neuropathy were present in 11 of 13 patients. Central nervous system involvement was found clinically in 3 of 13 patients. CONCLUSION: The surgical removal of the fatty tissue and abstinence from alcohol are essential for relieving the patients from functional impairment. Not only metabolic studies of lipid abnormalities but also a complete neurologic examination were required in order to improve the quality of life in MSL patients.

Immunoreactivity of CD99 in stomach cancer.

CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroectodermal tumor. Recently its immunoreactivity has also been reported in other tumors. However, the significance of CD99 isoforms expressed in these tumors has not been elucidated. In this study, we evaluated the expression of CD99 isoforms and its relationship with histopathologic parameters in gastric adenocarcinomas. Paraffin sections of 46 gastric adenocarcinomas were stained with an anti-CD99 monoclonal antibody, YG32. Twelve (26.1%) cases of 46 gastric adenocarcinomas showed immunoreactivity to YG32. The CD99 expression was also seen both in non-neoplastic foveolar epithelial cells and infiltrating lymphocytes. In addition, Western blot and RT-PCR analyses revealed that the type I is the predominant isoform of CD99 in non-neoplastic and neoplastic gastric tissues. The CD99 expression was usually seen in the intestinal type adenocarcinoma, while rarely in the diffuse type. The CD99 immunoreactivity decreased in MMP-2-overexpressing adenocarcinomas (p=0.028). Our results suggest that the type I is the major isoform of CD99 expressed in non-neoplastic gastric mucosa and gastric adenocarcinomas and its downregulation in gastric adenocarcinoma may be associated with cellular dedifferentiation and/or MMP-2 overexpression.

Phorbol 12-myristate 13-acetate up-regulates the transcription of MUC2 intestinal mucin via Ras, ERK, and NF-kappa B.

MUC2 is a secretory mucin normally expressed by goblet cells of the intestinal epithelium. It is overexpressed in mucinous type colorectal cancers but down-regulated in colorectal adenocarcinoma. Phorbol 12-myristate 13-acetate (PMA) treatment of colon cancer cell lines increases MUC2 expression, so we have undertaken a detailed analysis of the effects of PMA on the promoter activity of the 5'-flanking region of the MUC2 gene using stably and transiently transfected promoter reporter vectors. Protein kinase C inhibitors (bisindolylmaleimide, calphostin C) and inhibitors of mitogen-activated protein/extracellular signal regulated kinase kinase (MEK) (PD98059 and U0126) suppressed up-regulation of MUC2. Src tyrosine kinase inhibitor PP2, a protein kinase A inhibitor (KT5720), and a p38 inhibitor (SB 203580) did not affect transcription. Western blotting and reverse transcription-PCR analysis confirmed these results. In addition, co-transfections with mutants of Ras, Raf, and MEK showed that the induction of MUC2 promoter activity by PMA required these three signaling proteins. Our results demonstrate that PMA activates protein kinase C, stimulating MAP kinase through a Ras- and Raf-dependent mechanism. An important role for nuclear factor kappaB (NF-kappaB) was also demonstrated using the inhibitor caffeic acid phenethyl ester and electrophoretic mobility shift assays. Such identification of pathways involved in MUC2 up-regulation by PMA in the HM3 colon cancer cell line may serve as a model for the effects of cytokines and growth factors, which regulate MUC2 expression during the progression of colorectal cancer.