Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues.

A concise synthesis of pareitropone by oxidative cyclization of a phenolic nitronate is delineated. The use of TMSOTf as an additive to promote the facile formation of a strained norcaradiene intermediate provides convenient access to highly condensed multicyclic tropones in high yields. This synthesis is modular, efficient, and scalable, highlighting the synthetic utility of radical anion coupling reactions in annulation reactions. This work is discussed in the context of total syntheses of the tropoloisoquinoline alkaloids. Also included are the preparation of several congeners and a brief description of their biological activities.

Comparison of various anthropometric indices for the identification of a predictor of incident hypertension: the ARIRANG study.

We compared the predictive capability of weight, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), body mass index (BMI), body roundness index (BRI), and a body shape index (ABSI) to identify incident hypertension, and to determine whether any of these indices may be used as a better single predictor of incident hypertension. A total of 1718 participants aged 39-72 years were collected  in a longitudinal study. Logistic regression models were used to evaluate various anthropometric indices as significant predictors of hypertension. During 2.8 years of follow-up, 185 new cases of hypertension (10.8%) were reported. The BRI and ABSI were significantly higher in the participants who had developed hypertension than in those who had not (4.15 ± 1.01 vs. 3.57 ± 1.03, 0.80 ± 0.04 vs. 0.78 ± 0.05; respectively, p < 0.001). After adjusting for confounding variables, logistic regression analysis indicated that participants within the highest quartile of WC and WHtR were 4.79 and 4.51 times more likely to have hypertension than those within the lowest quartile (OR 4.79, 95% CI 2.49-9.20 vs. OR 4.51, 95% CI 2.41-8.43, respectively, p < 0.0001); in contrast, no such correlation was found for BMI, WHR, BRI, and ABSI. WC (AUC: 0.672) showed a more powerful predictive ability for hypertension (p < 0.0001) than BMI (AUC: 0.623), and an equal predictive power for hypertension as WHtR (AUC: 0.662) and BRI (AUC: 0.662) in the general population. We concluded that WC and/or WHtR but not BMI, showed superior prediction capability compared to WHR, BRI, and ABSI, for determining the incidence of hypertension in a community-based prospective study.

Vitrfication and Slow Freezing for Cryopreservation of Germinal Vesicle-Stage Human Oocytes: A Bayesian Meta-Analysis.

BACKGROUND: T he most commonly used methods for the cryopreservation of oocytes and embryos are vitrification and slow freezing. OBJECTIVE: The aim of this study was to to investigate whether there are differences in survival, in vitro maturation (IVM), and fertilization rates between cryopreserved immature oocytes, especially germinal vesicle (GV)-stage human oocytes, following vitrification and slow freezing. MATERIALS AND METHODS: A literature search was performed using the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases. A total of three studies were included in the Bayesian meta-analysis. RESULTS: There was no difference in survival rates between vitrification and slow freezing. Additionally, there was no difference in IVM rates and fertilization rates between vitrification and slow freezing. CONCLUSION: The superiority of vitrification over slow freezing for cryopreservation of GV-stage human oocytes remains unclear. Additional studies on cytoarchitecture and modification of the cryopreservation protocol are essential to achieve strong conclusions.

A combination of excimer laser treatment and topical tacrolimus is more effective in treating vitiligo than either therapy alone for the initial 6 months, but not thereafter.

BACKGROUND: There are insufficient data on the long-term outcome of a combination therapy that comprises phototherapy and topical administration of tacrolimus. AIM: To evaluate the clinical efficacy according to the duration of treatment and in vitro results of a combination therapy involving topical tacrolimus and an excimer laser in the treatment of vitiligo. METHODS: In total, 276 patients with nonsegmental vitiligo were treated with an excimer laser twice weekly, or with tacrolimus ointment twice daily, or both. The melanin contents and levels of melanogenic enzymes were measured in cultured human melanocytes treated with tacrolimus and/or excimer laser. RESULTS: After adjusting for potential confounders, the combination of tacrolimus plus excimer laser was significantly more effective than either tacrolimus or excimer laser alone (P < 0.001 and P < 0.01, respectively) for the first 6 months. However, this superiority was not observed after the initial 6 months of treatment. In vitro, the combination of tacrolimus plus excimer laser led to a higher level of melanogenesis than with either treatment alone. CONCLUSIONS: A combination treatment with topical tacrolimus and an excimer laser may be useful as an induction therapy for up to 6 months, but continuation of this therapy for > 6 months might not provide a better final outcome than monotherapy.

Human antibodies targeting the C-type lectin-like domain of the tumor endothelial cell marker clec14a regulate angiogenic properties in vitro.

It has been suggested that clec14a may be involved in tumor angiogenesis. However, a molecular mechanism has not been clearly identified. In this study, we show for the first time that C-type lectin-like domain (CTLD) of clec14a may be important for regulating cell migration and filopodia formation. Using phage display technology, recombinant human antibodies specific to the CTLDs of human and mouse clec14a (clec14a-CTLD (immunoglobulin G) IgG) were selected. Functional assays using the antibodies showed that clec14a-CTLD IgGs specifically blocked endothelial cell migration and tube formation without affecting cell viability or activation. Further, clec14a-CTLD IgGs inhibited clec14a-mediated cell-cell contact by blocking interaction between CTLDs. Finally, clec14a cross-linking by the clec14a-CTLD IgGs significantly downregulated clec14a expression on the surface of endothelial cells. These results strongly suggest that the clec14a-CTLD may be a key domain in angiogenesis, and that clec14a-CTLD IgGs specifically inhibit angiogenesis by modulating CTLD-mediated cell interactions and clec14a expression on the surface of endothelial cells.

Population-specific spectrum of the F11 mutations in Koreans: evidence for a founder effect.

The aim of this study was to investigate a mutation spectrum of F11 among Korean patients with factor XI (FXI) deficiency and to determine the haplotypes of mutations frequently found in Koreans. Thirteen unrelated patients from non-consanguineous families with FXI deficiency were included in the study. In the mutation analysis, the most frequently found mutations were Q263X (four cases; 31%) and Q226X (three cases; 23%). The frequency of Q263X-bearing haplotype was significantly different between normal and patient groups (p = 0.001), which is consistent with a founder effect of Q263X mutation. Testing for the presence of these two mutations should be the first genetic screening in Korean patients with FXI deficiency.

Osteolytic mandible presenting as an initial manifestation of an adult acute lymphoblastic leukaemia.

A case of adult acute lymphoblastic leukaemia is reported. A 35-year-old male presented with an osteolytic lesion of the mandible. There was no definitive involvement in other craniofacial bones. A panoramic radiograph taken 4 months previously showed no bony involvement. A complete blood count showed a slightly decreased red blood cell count, but normal white blood cell count, white blood cell differential count and platelet count. Routine chemistry revealed hypercalcemia with an increased level of parathyroid hormone-related protein. Histopathological examination of bone marrow biopsy confirmed the diagnosis of acute lymphoblastic leukaemia.

Effect of leptin on differentiation of human dental stem cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) were identified in adult human periodontal ligament and dental pulp that are considered as potential stem cell sources for future clinical applications in dentistry. Leptin is known as an important regulator of mesenchymal differentiation. The objective of this study was to elucidate the role of leptin on proliferation and differentiation of dental MSCs. MATERIALS AND METHODS: Enhancement of cemento/odontoblastic differentiation of dental stem cells by leptin was confirmed by alizarin red S staining and alkaline phosphatase activity staining. In contrast, leptin reduced adipogenesis in both dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) confirmed by oil red O staining and RT-PCR. The expression of adipogenic markers, lipoprotein lipase and proliferator-activated receptor γ2 (PPARγ2), were suppressed in PDLSCs incubated on media supplemented with leptin for 2 weeks. RESULTS: Leptin had a relatively stronger osteogenesis promoting effect and adipogenesis suppressing effect in PDLSCs than in DPSCs. CONCLUSIONS: Collectively, leptin had a relatively stronger promoting effect on cemento/odontoblastic differentiation and a suppressing effect on adipogenesis in PDLSCs than in DPSCs. This study has provided evidence that leptin acts as an important modulator of dental MSCs differentiation.

Impact of lifestyle factors on colorectal polyp detection in the screening setting.

BACKGROUND: Awareness of risk factors for colorectal neoplasia could address risk reduction strategies in asymptomatic subjects. METHODS: This is a post hoc analysis of a prospective, cross-sectional study of 1321 asymptomatic adults. All the subjects underwent same-day CT colonography and colonoscopy to determine the prevalence of colorectal neoplasia. The variables examined included body mass index, smoking, alcohol consumption, age, and gender. Univariate and logistic regression analyses were performed for detection of colorectal neoplasia and hyperplastic polyps. Odds ratios with 95% confidence intervals were calculated. RESULTS: Colorectal adenomas and hyperplastic polyps were detected in 378 (28.6%) and 157 (11.9%) participants, respectively. In both univariate and multivariate analysis, increasing age, male gender, and body mass index > or =25 were significantly associated with the detection of colorectal adenomas, with an odds ratio of 1.22 (95% CI,1.09-1.36), 1.28 (95% CI, 1.06-1.45), and 1.34 (95% CI, 1.02-1.77), respectively. A history of smoking was the only identifiable risk factor for hyperplastic polyps (odds ratio, 1.98; 95% CI, 1.41-2.78). CONCLUSIONS: Body mass index > or =25, increasing age, and male gender were all associated with an increased likelihood of colorectal adenomas at screening, whereas smoking was strongly associated with hyperplastic polyps.

Evaluation of the biodurability of polyurethane-covered stent using a flow phantom.

OBJECTIVE: To evaluate the biodurability of the covering material in retrievable metallic stents covered with polycarbonate polyurethane. MATERIALS AND METHODS: Using a peristaltic pump at a constant rate of 1 ml/min, bile was recirculated from a reservoir through a long tube containing four stents. Each of these was removed from the system every two weeks and a radial tensile strength test and scanning electron microscopy (SEM) were performed. Each stent, removed at 2, 4, 6 and 8 weeks, was compared with a control stent not exposed to bile juice. RESULTS: Gross examination showed that stents were intact at 2 weeks, but at 4, 6 and 8 weeks cracks were observed. The size of these increased gradually in accordance with the duration of exposure, and at 8 weeks several large holes in the polyurethane membrane were evident. With regard to radial tensile strength, extension and peak load at break were 84.47% and 10.030 N/mm, 54.90% and 6.769 N/mm, 16.55% and 2.452 N/mm, 11.21% and 1.373 N/mm at 0, 2, 4 and 6 weeks, respectively. Scanning electron microscopy at 2 weeks revealed intermittent pitting and cracking, and examination at 4, 6 and 8 weeks showed that the size of these defects was gradually increasing. CONCLUSION: When the polyurethane membrane was exposed to bile, biodegradation was first observed at week two and increased gradually according to the duration of exposure.

A case of del(13)(q22) with multiple major congenital anomalies, imperforate anus and penoscrotal transposition.

"13q-"syndrome is known to have widely variable manifestations, including retinoblastoma, mental & growth retardation, malformation of brain & heart, anal atresia, and anomalies of the face and limbs. Here we report a case of del(13)(q22) with multiple major congenital anomalies for the first time in Korea. The patient was born at 36(+4) weeks of pregnancy by caesarian section. Birth weight was 1490g. On examination the following features were noted: - imperforate anus, ambiguous genitalia (bifid scrotum, penoscrotal transposition, hypospadia), syndactyly of toes, absence of thumbs, abnormal facies (dolichocephaly, telecanthus, large low set ears, saddle nose, high arched palate, micrognathia). Neurocranial ultrasonography showed atrophy of the corpus callosum and multiple calcifications. He died at 14 days. Post-mortem autopsy findings showed cholestasis and fatty metamorphosis of liver, abnormal lobulation (Rt:2, Lt:1) and lymphangiectasis of the lung, VSD, ASD, PDA of heart, and acute tubular necrosis of kidney. Cytogenetic studies was confirmed to 46,XY,del(13) (q22) by Giemsa banded chromosomes from peripheral blood lymphocytes.

Structure-activity relationships of apio nucleosides as potential antiviral agents.

Several types of novel apio nucleosides were synthesized starting from 1,3-dihydroxyacetone and evaluated for antiviral activity. Among compounds tested, amino substituted apio dideoxynucleosides exhibited anti-HBV activity, while thioapio dideoxynucleosides were found to be active against HIV-1. Apio dideoxydidehydro nucleosides showed moderate to potent anti-HCMV activity, but their bioisosteric thioapio dideoxydidehydro nucleosides did not exhibit any significant antiviral activity.

A novel silent substitution (C8516T) in exon 9 of the human PROC gene.

Protein C is a vitamin K dependent serine protease zymogen, which has a regulatory influence over the coagulation cascade via the inhibition of factors Va and VIIIa. Hereditary protein C deficiency is associated with an increased risk of thromboembolic disease. A multitude of families displaying protein C (PROC) gene defects have been reported, and a number of DNA sequence polymorphisms are known to occur in the PROC gene. We have identified a previously undescribed silent substitution (C8516T) by direct DNA sequencing in a Korean patient with thrombosis and protein C deficiency. In addition, a rare T allelic frequency (0.016) was determined in 123 patients with acquired or hereditary protein C deficiency.

Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age.

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.

Evidence for two modes of allelic loss: multifocal analysis on both early and advanced gastric carcinomas.

To assess the extent and the timing of allelic loss required for the progression of gastric carcinoma, the intratumoral distribution of loss of heterozygosity (LOH) was compared in early and advanced tumors: early loss is uniformly observed in all tumor areas and late loss is localized in parts of tumor tissue. Tumor sites (167 sites) obtained from 42 gastric carcinoma tissues (26 advanced cancers and 16 early cancers) were examined for LOH on chromosomes 5q, 9p, 13q, 17p, and 18q. By using two or three microsatellite markers for each chromosome arm, it was shown that of 29 tumors showing LOH in at least one tumor site, 15 (51.7%, 12 advanced and three early cancers) harbored multiple losses on three or more chromosome arms, and 89.4% (84 of 94) of these losses was uniformly found in all tumor sites tested. In the remaining 14 tumors (48.3%, eight advanced and six early tumors) with sporadic losses on one or two chromosome arms, 44% (11 of 25) of the losses were commonly shared among the sites tested. Such marked difference (P<0.001, Fisher's exact test) in the intratumoral distribution of multiple and sporadic LOH patterns proposes two distinct LOH subtypes: multiple losses (high LOH), occurring at an early stage with a few additional losses, and sporadic losses (low LOH), taking place relatively late during tumor progression. The multifocal LOH findings imply that, rather than being gradual, the allelic losses take place in two manners that are already determined at an early stage.