Gender-specific association of androgenetic alopecia with metabolic syndrome in a middle-aged Korean population.

BACKGROUND: Although several previous studies have investigated the association between metabolic syndrome (MetS) and androgenetic alopecia (AGA), the study results have been inconsistent. OBJECTIVES: The aim of this study was to investigate the relationship between the presence of MetS and AGA according to gender in a middle-aged Korean population. METHODS: A population-based cross-sectional study was conducted on a sample from the Korean Genome Epidemiology Study. In total, 3408 subjects (1707 men and 1701 women) were enrolled between January 2008 and February 2010. The Norwood classification for men and Ludwig classification for women were used for assessment of the degree of hair loss. Information on components of MetS together with other possible risk factors was collected. RESULTS: In men, the risk of having Norwood type IV or greater was not increased for subjects with MetS compared with those without MetS. In women, the risk of having Ludwig type I or greater was significantly increased for subjects with MetS compared with those without MetS after controlling for age and smoking status (OR 1.68, 95% CI 1.14-2.48; P=0.01). Similar results were also observed for the number of fulfilled components of MetS [odds ratio (OR) 1.38, 95% confidence interval (CI) 1.00-1.91; P<0.05]. When each component of MetS was considered individually, associations between AGA and all five components of MetS (waist circumference, triglycerides, high-density lipoprotein-C, blood glucose, and blood pressure) were not statistically significant. When multiple regression was used to adjust for age, family history and smoking, there was no significant association between the prevalence of MetS and moderate to severe AGA in the male group. On the contrary, a statistically significant positive association was noted between the prevalence of MetS and AGA in the female group. CONCLUSIONS: Our analysis of AGA and the prevalence of MetS in a large population-based cohort demonstrated quite different findings compared with previous reports. The different results according to gender suggest that there may be different mechanisms that are yet to be defined between male and female AGA.

The land use plan and water quality prediction for the Saemangeum reclamation project.

As the final closure of the world's longest sea dike of 33 km, the use of the Saemangeum reclaimed land becomes an issue in Korea. The Korean government has proclaimed that the Saemangeum Reclamation Project will be handled in an environmentally friendly manner but its effect on the water quality of reservoirs has always been controversial. This study was conducted to estimate the water quality of the Saemangeum reservoir using WASP5 according to the new land use plan adopted in 2007. Predictions on water quality shows that Dongjin reservoir would meet the standards for COD, T-P, and Chl-a if the wastewater from the Dongjin region was properly managed. However, T-P and Chl-a in Mangyeong reservoir would exceed the standards even without releasing the treated wastewater into the reservoir. With further reductions of 20% for T-P and Chl-a from the mouth of Mangyeong river, the water quality standards in the reservoir were achieved. This means that additional schemes, as well as water quality management programs established in the Government Master Plan in 2001, should be considered. Although the Saemangeum reservoir would manage to achieve the standards, it will enter a eutrophic state due to the high concentration of nutrients.

Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia.

Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adeno-associated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia.

Parathion degradation and toxicity reduction in solar photocatalysis and photolysis.

The solar photocatalytic degradation of methyl parathion was investigated using a circulating TiO2/solar light reactor. Under solar photocatalysis condition, parathion was more effectively degraded than solar photolysis and TiO2-only conditions. With solar photocatalysis, 20 mg/L of parathion was completely degraded within 60 min with a TOC decrease of 63% after 150 min. The main ionic byproducts during photocatalysis recovered from parathion degradation were mainly as NO3-, NO2- and NH4+, 80% of the sulphur as SO4(2-), and 5% of phosphorus as PO4(3-). The organic intermediates 4-nitrophenol and methyl paraoxon were also identified, and these were further degraded in solar photocatalytic condition. Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the acute toxicity of solutions treated by solar photocatalysis and photolysis. The Microtox test using V. fischeri showed that the toxicity expressed as EC50 (%) value increased from 5.5% to >82% in solar photocatalysis, indicating that the treated solution is non-toxic, but only increased from 4.9 to 20.5% after 150 min in solar photolysis. The acute toxicity test using D. magna showed that EC50 (%) increased from 0.05 to 1.08% under solar photocatalysis, but only increased to 0.12% after 150 min with solar photolysis, indicating the solution is still toxic. The pattern of toxicity reduction parallels the decrease in TOC and the parathion concentrations.

Early wound complications in advanced head and neck cancer treated with surgery and Ir 192 brachytherapy.

OBJECTIVES: Brachytherapy, either as primary or adjuvant therapy, is increasingly used to treat head and neck cancer. Reports of complications from the use of brachytherapy as adjuvant therapy to surgical excision have been limited and primarily follow Iodine 125 (I125) therapy. Early complications include wound breakdown, infection, flap failure, and sepsis, and late complications may include osteoradionecrosis, bone marrow suppression, or carotid injuries. The authors sought to identify the early wound complications that follow adjuvant interstitial brachytherapy with iridium 192 (IrS92). STUDY DESIGN: A retrospective chart review of all patients receiving adjuvant brachytherapy at a tertiary medical center over a 4-year period. METHODS: Nine patients receiving Ir192 brachytherapy via afterloading catheters placed during surgical resection for close or microscopically positive margin control were evaluated. It was used during primary therapy in six patients and at salvage surgery in three. Early complications were defined as those occurring within 6 weeks of surgical therapy. RESULTS: The overall complication rate was 55% (5/9), and included significant wound breakdown in two patients, minor wound dehiscence in three, and wound infection, bacteremia, and local tissue erosion in one patient each. All complications occurred in patients receiving flap reconstruction and one patient required further surgery to manage the complication. Complication rates were not associated with patient age, site, prior radiotherapy, timing of therapy, number of catheters, or dosimetry. CONCLUSIONS: The relatively high complication rate is acceptable, given the minor nature of most and the potential benefit of radiotherapy. Further study should be undertaken to identify those patients who will achieve maximum therapeutic benefit without prohibitive local complications.

Adenovirus calcium phosphate coprecipitates enhance squamous cell carcinoma gene transfer.

OBJECTIVES/HYPOTHESIS: Adenoviral-mediated gene transfer offers a potential new treatment strategy for squamous cell cancer of the head and neck (SCCHN). Initial studies on some SCCHN cell lines have shown that these cells can be resistant to adenovirus-mediated gene transfer, requiring large amounts of vector and long infection times. The objectives of this study were to identify the barriers to gene transfer in three SCCHN lines, FaDu, SCC-9, and SCC-15, and to develop a method to circumvent the obstacles. We hypothesized that a low expression of adenovirus receptors may limit adenovirus infection and this may be overcome by using adenovirus complexed with calcium phosphate coprecipitates. METHODS: Using standard cell and molecular biology techniques, the infectability of SCCHN cells was investigated. RESULTS: Using Cy3-labeled adenovirus, we found minimal binding of adenovirus to FaDu cells and variable levels of binding among SCC-9 and SCC-15 cells. Northern blot analysis indicated that messenger RNA (mRNA) transcripts for coxsackie-adenovirus receptor, which binds adenovirus, were absent in FaDu cells but present in SCC-9 and SCC-15 cells. Integrin alphavbeta5, which binds and facilitates internalization of adenovirus, were expressed at low levels in all three cell types. We overcame these barriers by using adenovirus complexed with calcium phosphate precipitates. Total transgene expression and the number of cells expressing transgene were increased in all three cancer lines using adenovirus complexed with calcium phosphate precipitates compared with adenovirus that was not complexed. CONCLUSIONS: Data in the present study suggest that adenovirus-mediated gene transfer to SCCHN cell lines is a result of limited viral receptors. Delivering adenovirus in a calcium phosphate coprecipitate enhanced gene transfer and, perhaps, the therapeutic index.

Lectin binding and endocytosis at the apical surface of human airway epithelia.

The specificity of lectin binding to distinct saccharides makes them valuable reagents for investigation and identification of cells within complex tissues and potentially for delivery of agents into cells. Therefore we examined lectin binding to airway epithelia. We used an in vitro model of primary cultures of well-differentiated human airway epithelia and applied the lectins to the apical surface of living epithelia. This approach limited binding specifically to the extracellular surface of the apical membrane. Of 32 lectins studied, we found 15 that bound to the apical membrane. The pattern varied from diffuse binding to the surface of nearly all the cells, to binding to a small subset of the cells. Our data combined with earlier studies identify lectins that may be used to detect specific populations of epithelial cells. Because lectins may be used to deliver a variety of agents, including gene transfer vectors, to airway cells, we examined endocytosis of lectins. We found that several lectins bound to the apical surface were actively taken up into the cells. These data may be of value for studies of airway epithelial structure and may facilitate the targeting of the epithelial apical surface.

Frequent loss of chromosome arm 1p DNA in parathyroid adenomas.

Two molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of the PRAD1/cyclin D1 oncogene and allelic loss of chromosome 11 DNA, often including the multiple endocrine neoplasia type 1 (MEN1) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor-specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for 1 or more of the 9 chromosome 1 markers examined. Allelic loss at 1 or more of these informative loci on chromosome 1 was observed in 10 of 25 (40%) adenomas. Although many tumors lost extensive regions on chromosome 1, all but one of these tumors had allelic loss of distal 1p (1p32-pter); four tumors also lost loci on 1q. Allelic loss at 11q13, the site of the MEN1 gene, was detected in 5 of 21 (24%) informative cases, including 3 with 1p loss. In contrast, allelic loss was rarely observed at loci on 9q and 10p and was not observed at loci on 3p, 3q, 4p, 5q, 12q, 14q, 18q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm 1p is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on 1p commonly contributes to their pathogenesis.

Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer.

Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. Whereas AAV serotype 2-mediated gene transfer to muscle has partially replaced factor IX deficiency in hemophilia patients, its ability to mediate gene transfer to the lungs for cystic fibrosis is hindered by lack of apical receptors. However, AAV serotype 5 infects human airway epithelia from the lumenal surface. We found that in contrast to AAV2, the apical membrane of airway epithelia contains abundant high affinity receptors for AAV5. Binding and gene transfer with AAV5 was abolished by genetic or enzymatic removal of sialic acid from the cell surface. Furthermore, binding and gene transfer to airway epithelia was competed by lectins that specifically bind 2,3-linked sialic acid. These observations suggest that 2,3-linked sialic acid is either a receptor for AAV5 or it is a necessary component of a receptor complex. Further elucidation of the receptor for this virus should enhance understanding of parvovirus biology and expand the therapeutic targets for AAV vectors.

Apical localization of the coxsackie-adenovirus receptor by glycosyl-phosphatidylinositol modification is sufficient for adenovirus-mediated gene transfer through the apical surface of human airway epithelia.

In well-differentiated human airway epithelia, the coxsackie B and adenovirus type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This location may explain the observation that gene transfer is inefficient when adenovirus vectors are applied to the apical surface. To further test this hypothesis and to investigate requirements and barriers to apical gene transfer to differentiated human airway epithelia, we expressed CAR in which the transmembrane and cytoplasmic tail were replaced by a glycosyl-phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs enhanced gene transfer with similar efficiencies in fibroblasts. In airway epithelia, GPI-CAR localized specifically to the apical membrane, where it bound adenovirus and enhanced gene transfer to levels obtained when vector was applied to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway epithelia, correcting the Cl(-) transport defect. In contrast, when we expressed wild-type CAR it localized to the basolateral membrane and failed to increase apical gene transfer. Only a small amount of Tailless-CAR resided in the apical membrane, and the effects on apical virus binding and gene transfer were minimal. These data indicate that binding of adenovirus to an apical membrane receptor is sufficient to mediate effective gene transfer to human airway epithelia and that the cytoplasmic domain of CAR is not required for this process. The results suggest that targeting apical receptors in differentiated airway epithelia may be sufficient for gene transfer in the genetic disease cystic fibrosis.