Explorations with Polycarbocyclic Cage Compounds

A variety of novel cage-functionalized pyridyl containing crown ethers have been prepared for use in selective alkali metal complexation studies. A highly preorganized, cage-functionalized cryptand also has been designed and has been synthesized for use as a selective Li+ complexant. The alkali metal picrate extraction profiles of these cage-functionalized crown ethers also have been studied. Novel cage-functionalized diazacrown ethers have been prepared for selective alkali metal complexation studies. Alkali metal picrate extraction experiments have been performed by using this new class of synthetic ionophores to investigate the effects of cage-annulation and the influence of N-pivot lariat sidearms upon their resulting complexation properties. Novel pyridyl containing calix[4]arene receptors were prepared. Analysis of their respective 1H NMR and 13C NMR spectra suggests that calix[4]arene moieties in the ligand occupy the cone conformation. The complexation properties of these host molecules were estimated by performing a series of alkali metal picrate extraction experiments. An optically active cage-functionalized crown ether which contains a binaphthyl moiety as the chiral unit was prepared. The ability of the resulting optically active crown ether to distinguish between enantiomers of guest ammonium ions (i.e., phenylethylamonium and phenylglycinate salts) in transport experiments was investigated. Hexacyclo[11.2.1.02,12.05,10.05,15.010,14]hexadeca-6,8-diene-4,11-dione was prepared from hexacyclo[7.4.2.01,9.03,7.04,14.06,15] pentadeca-10,12-diene-2,8-dione. Unanticipated but remarkable acid and base promoted rearrangements of this new cage dione to novel polycyclic systems were observed and subsequently were investigated. The structures of the new systems thereby obtained were determined unequivocally by application of X-ray crystallographic methods. It is noteworthy that the reactions reported herein each provide the corresponding rearranged product in high yield in a single synthetic step. Pi-facial and regioselectivity in the thermal Diels-Alder cycloaddition between hexacyclo[11.2.1.02,12.05,10.05,15.010,14]hexadeca-6,8-diene- 4,11-dione and ethyl propiolate have been explored. This reaction proceeds via stereospecific approach of the dienophile toward the syn face of the diene p -system. However, [4+2]cycloaddition proceeds with only modest proximal/distal regioselectivity. The structure of the minor reaction product was established unequivocally via application of X-ray crystallographic techniques

π-Facial Selectivity in Diels-Alder Cycloadditions

Diels-Alder reactions between π-facially differentiated dienes and/or π-facially differentiated dienophiles frequently proceed with remark-able π-facial selectivity. Experimental and theoretical studies have been undertaken in an effort to gain insight into the fundamental origins of this phenomenon. Reactions of interest in this connection include thermal [4 + 2] cycloadditions between (i) various dienophiles and cage-annulated 1,3-cyclohexadienes (i.e. systems 1, 4, 6, and 9) and (ii) various dienes and cage-annulated dienophiles (i.e. systems 1a, 11a, and 14). The results of relevant molecular mechanics, semiempirical, and ab initio molecular orbital calculations generally are consistent with experiment

Novel chelating agents for zirconium-89-positron emission tomography (PET) imaging: Synthesis, DFT calculation, radiolabeling, and in vitro and in vivo complex stability

We report the synthesis and evaluation of novel chelating agents for zirconium-89

Incidence and Risk Factors of Insulin Resistance Syndrome in 20-59 Year-Old Korean Male Workers

We investigated the incidence of insulin resistance syndrome (IRS) according to the criteria of diagnoses suggested by the American College of Endocrinology/American Association of Clinical Endocrinologists and the risk factors associated with the development of IRS. Among 2,048 subjects without a history of/or drug treatment for hypertension, diabetes, dyslipidemia with normal findings at baseline, 1,578 subjects aged 20-59 yr were followed prospectively for 2 yr. The incidence of IRS was 6.9 per 100 persons/year. The relative risk (RR) due to age was 1.03 (95% CI: 1.00-1.05) with every one-year increase in age. The RR associated with an abnormal waist-hip ratio group (≥0.9) was increased by 1.74 (95% CI:1.17-2.58) compared to the normal group (<0.9); RR associated with abnormal alanine transferase was increased (≥35 IU/L) by 1.70 (95% CI: 1.20-2.41) compared to the normal group (<35 IU/L); and the RR associated with abnormal low-density lipoprotein (LDL) cholesterol was increased (≥160 mg/L) by 1.70 (95% CI: 1.19-2.44) compared to the normal LDL cholesterol (<160 mg/L). Lastly, the RR of current smokers was increased by 1.63 (95% CI: 1.09-2.42) compared to that of non-smokers. It is necessary to develop methods of prevention and therapeutic approach to manage the integrated risk factors as opposed to individual factors

Genome-edited HEADING DATE 3a knockout enhances leaf production in Perilla frutescens

Environmental cues regulate the transition of many plants from vegetative to flowering development. Day length, or photoperiod, is one cue that synchronizes flowering by changing seasons. Consequently, the molecular mechanism of flowering control is prominent in Arabidopsis and rice, where essential genes like FLOWERING LOCUS T (FT) homolog, HEADING DATE 3a (Hd3a), have been connected to flowering regulation. Perilla is a nutrient-rich leaf vegetable, and the flowering mechanism remains largely elusive. We identified flowering-related genes under short-day conditions using RNA sequencing to develop an enhanced leaf production trait using the flowering mechanism in the perilla. Initially, an Hd3a-like gene was cloned from the perilla and defined as PfHd3a. Furthermore, PfHd3a is highly rhythmically expressed in mature leaves under short-day and long-day conditions. Ectopic expression of PfHd3a in Atft-1 mutant plants has been shown to complement Arabidopsis FT function, resulting in early flowering. In addition, our genetic approaches revealed that overexpression of PfHd3a in perilla caused early flowering. In contrast, the CRISPR/Cas9 generated PfHd3a-mutant perilla showed significantly late flowering, resulting in approximately 50% leaf production enhancement compared to the control. Our results suggest that PfHd3a plays a vital role in regulating flowering in the perilla and is a potential target for molecular breeding in the perilla

Solitary Primary Gastric Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a relatively rare subgroup of non-Hodgkin's lymphoma that is characterized by an aggressive and severe disease course with frequent involvement of regional lymph nodes and/or early metastasis. Because most cases of MCL are diagnosed in the advanced stages, clinical data on extranodal or early stage MCL is lacking, and MCL that is both extranodal and diagnosed during the early stages is even more rare. There have been several case reports on primary gastric MCL, which comprise a type of extranodal MCLs. However, to our knowledge, there have been no reports on solitary primary gastric MCL without regional lymph node involvement or distant metastasis. Recently, the authors experienced an uncommon case of MCL with the aforementioned characteristics that was managed with chemotherapy followed by allogenic stem cell transplantation

Candida haemulonii and Closely Related Species at 5 University Hospitals in Korea: Identification, Antifungal Susceptibility, and Clinical Features

Background. Candida haemulonii, a yeast species that often exhibits antifungal resistance, rarely causes human infection. During 2004-2006, unusual yeast isolates with phenotypic similarity to C. haemulonii were recovered from 23 patients (8 patients with fungemia and 15 patients with chronic otitis media) in 5 hospitals in Korea. Methods. Isolates were characterized using D1/D2 domain and ITS gene sequencing, and the susceptibility of the isolates to 6 antifungal agents was tested in vitro. Results. Gene sequencing of the blood isolates confirmed C. haemulonii group I (in 1 patient) and Candida pseudohaemulonii (in 7 patients), whereas all isolates recovered from the ear were a novel species of which C. haemulonii is its closest relative. The minimum inhibitory concentration (MIC) ranges of amphotericin B, fluconazole, itraconazole, and voriconazole for all isolates were 0.5-32 mu g/mL (MIC(50), 1 mu g/mL), 2-128 mu g/mL (MIC(50), 4 mu g/mL), 0.125-4 mu g/mL (MIC(50), 0.25 mu g/mL), and 0.03-2 mu g/mL (MIC(50), 0.06 mu g/mL), respectively. All isolates were susceptible to caspofungin (MIC, 0.125-0.25 mu g/mL) and micafungin (MIC, 0.03-0.06 mu g/mL). All cases of fungemia occurred in patients with severe underlying diseases who had central venous catheters. Three patients developed breakthrough fungemia while receiving antifungal therapy, and amphotericin B therapeutic failure, which was associated with a high MIC of amphotericin B (32 mu g/mL), was observed in 2 patients. Conclusions. Candida species that are closely related to C. haemulonii are emerging sources of infection in Korea. These species show variable patterns of susceptibility to amphotericin B and azole antifungal agents.Shin JH, 2007, J CLIN MICROBIOL, V45, P2385, DOI 10.1128/JCM.00381-07Khan ZU, 2007, J CLIN MICROBIOL, V45, P2025, DOI 10.1128/JCM.00222-07Lee JS, 2007, J CLIN MICROBIOL, V45, P1005, DOI 10.1128/JCM.02264-06Pfaller MA, 2006, J CLIN MICROBIOL, V44, P819, DOI 10.1128/JCM.44.3.819-826.2006Sugita T, 2006, MICROBIOL IMMUNOL, V50, P469Clancy CJ, 2005, ANTIMICROB AGENTS CH, V49, P3171, DOI 10.1128/AAC.49.8.3171-3177.2005Odds FC, 2004, J CLIN MICROBIOL, V42, P3475, DOI 10.1128/JCM.42.8.3475-3482.2004Rodero L, 2002, J CLIN MICROBIOL, V40, P2266, DOI 10.1128/JCM.40.6.2266-2269.2002*CLSI, 2002, M27A2 CLSISugita T, 1999, J CLIN MICROBIOL, V37, P1985Pfaller MA, 1998, DIAGN MICR INFEC DIS, V32, P223Nguyen MH, 1998, J INFECT DIS, V177, P425Kurtzman CP, 1997, J CLIN MICROBIOL, V35, P1216LEHMANN PF, 1993, J CLIN MICROBIOL, V31, P1683GARGEYA IB, 1991, J MED VET MYCOL, V29, P335

Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009

PurposeHand-foot-mouth disease (HFMD) is a common viral illness in children, which is usually mild and self-limiting. However, in recent epidemics of HFMD in Asia, enterovirus 71 (EV71) has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. HFMD was epidemic in Korea in the spring of 2009. Severe cases with complications including death have been reported. The clinical characteristics in children with neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong Hospital.MethodsExaminations for EV71 were performed from the stools, respiratory secretion or CSF of children who presented neurologic symptoms associated with HFMD by realtime PCR. Clinical and radiologic data of the patients were collected and analyzed.ResultsEV71 was isolated from the stool of 16 patients but not from respiratory secretion or CSF. Among the 16 patients, meningitis (n=10) was the most common manifestation, followed by Guillain-Barré syndrome (n=3), meningoencephalitis (n=2), poliomyelitis-like paralytic disease (n=1), and myoclonus (n=1). Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008.ConclusionBecause EV71 causes severe complications and death in children, a surveillance system to predict upcoming outbreaks should be established and maintained and adequate public health measures are needed to control disease

Risk factors for bone mineral density at the calcaneus in 40–59 year-old male workers: A cross-sectional study in Korea

<p>Abstract</p> <p>Background</p> <p>Few epidemiologic studies have attempted to investigate the prevalence and risk factors for osteopenia and osteoporosis in middle-aged Asian men. We performed this study to determine the prevalence and risk factors of osteopenia and osteoporosis in this population.</p> <p>Methods</p> <p>This cross-sectional study was conducted from March to July, 2004. The subjects were 2,073 males aged from 40 to 59 years in the KHNP (Korea Hydro & Nuclear Power) workplace-based cohort. Bone mineral density (BMD) was measured by peripheral, dual-energy, X-ray absorptiometry (DXA) at the calcaneus. Anthropometric and lifestyle factors were investigated using a standard, self-reported questionnaire.</p> <p>Results</p> <p>BMD was 0.60 ± 0.09 g/cm²(mean ± standard deviation) and was negatively correlated with age (r = -0.18, <it>P </it>< 0.001), but positively correlated with waist-to-hip ratio (WHR; r = 0.15, <it>P </it>< 0.001), body fat (r = 0.10, <it>P </it>< 0.001), BMI (r = 0.35, <it>P </it>< 0.001), height (r = 0.26, <it>P </it>< 0.001), and weight (r = 0.43, <it>P </it>< 0.001).</p> <p>In multiple linear regression analysis, the independent determinants associated with BMD were increasing age (coefficient = -0.002, <it>P </it>< 0.001), physical activity (≤ 2/week vs. ≥ 3/week; coefficient = 0.017, <it>P </it>< 0.001), WHR (coefficient = -0.796, <it>P </it>< 0.001), body mass index (BMI; coefficient = 0.023, <it>P </it>< 0.001) and smoking status (never vs. ever; coefficient = -0.018, <it>P </it>< 0.001).</p> <p>Conclusion</p> <p>We suggest that BMD of the calcaneus is correlated negatively with exposure to smoke and increased WHR, but positively with regular exercise and increased BMI.</p

Prevalence of Neuropathic Pain and Patient-Reported Outcomes in Korean Adults with Chronic Low Back Pain Resulting from Neuropathic Low Back Pain

Study DesignA noninterventional, multicenter, cross-sectional study.PurposeWe investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP).Overview of LiteratureAmong patients with CLBP, 20%–55% had NP.MethodsPatients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4<4) groups.ResultsA total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%–43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p<0.01), in patients who had pain based on radiological and neurological findings (59.0%; p<0.01), and in patients who had severe pain (49.0%; p<0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p<0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p<0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (β=−0.1; p<0.01) and higher QBPDS (β=7.0; p<0.01) scores than those without NP.ConclusionsNP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP