Comparative study of new autologous material, bone-cartilage composite graft, for ossiculoplasty with Polycel® and Titanium.

OBJECTIVE: Ossiculoplasty is a surgical procedure that recreates sound transmission of the middle ear in conductive hearing loss. Various materials have been used for ossicular reconstruction, but the most ideal material for ossiculoplasty remains controversial. The purpose of this study was to introduce a novel method of autologous ossiculoplasty, bone-cartilage composite graft (BCCG) and to compare its surgical results with different types of ossiculoplastic prostheses. STUDY DESIGN: A retrospective study was performed in a tertiary referral centre. METHODS: Data of 275 patients who received ossiculoplasty using the three different materials of BCCG, Polycel® and titanium were analysed according to type of ossiculoplasty: partial or total ossicular replacement prosthesis (PORP or TORP). Hearing results, complication rates and clinical parameters including age, sex, past history, preoperative diagnosis and surgery type were compared among different groups. RESULTS: Ossiculoplasty with BCCG showed satisfactory hearing outcomes and the lowest complication rate among the three different materials. In particular, its extrusion rate was 0%. CONCLUSION: We propose that the BCCG technique is a useful alternative method for ossiculoplasty, with proper patient selection.

Licoricidin, an isoflavonoid isolated from Glycyrrhiza uralensis Fisher, prevents UVA-induced photoaging of human dermal fibroblasts.

OBJECTIVE: Licoricidin is an isoflavonoid isolated from Glycyrrhiza uralensis Fisher. In this study, we investigated the effects of licoricidin on photoaging of UVA-irradiated human dermal fibroblasts (HDFs). METHODS: In vitro reactive oxygen species (ROS) scavenging activity, cellular protective effect and inhibition of elastase activity was determined by Fe3+ -EDTA/H2 O2 systems, photohaemolysis and elastase activity assay, respectively. Anti-oxidative capacity of the compound was evaluated by fluorescent ELISA and 2', 7'-dichlorofluorescin-diacetate (DCF-DA) assay. The expression of protein and phosphorylation was examined using Western blot. RESULTS: The ROS scavenging activity (OSC50 ) of licoricidin was 2.77 µM. It was 3.1-fold higher than that of L-ascorbic acid. Its protective effects were confirmed in a study of 1 O2 -induced cellular damage to human erythrocytes. The τ50 value of 10 µM of licoricidin was 71.0 min; this was markedly higher than that obtained with α-tocopherol (37.0 min). The elastase inhibitory activity of licoricidin (IC50 of 61.2 µM) was 2.1-fold more potent than that of oleanolic acid. Licoricidin markedly reduced the UVA-induced intracellular ROS in a concentration-dependent manner. Western blot revealed that licoricidin attenuated the UVA-dependent induction of MMP-1 protein. Mechanistically, this appeared to be due to licoricidin-dependent inhibition of mitogen-activated protein kinases (MAPK) phosphorylation, which resulted in decreased c-Jun activation and reduced c-Jun and c-Fos expression. CONCLUSION: Licoricidin blocks UVA-induced photoaging via ROS scavenging. This activity converges to limit the activity of MMP-1. These data suggest that licoricidin may be considered as an active ingredient in new topically applied anti-ageing formulations.

Blue Emitters Based on Aryl End-Capped Pyrene Groups for OLEDs.

We have synthesized four pyrene-derived blue emitting materials using Suzuki cross coupling reactions. All OLED devices using these materials as emitting materials showed efficient blue electroluminescence (EL). Particularly, a device using 1,1'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis-pyrene (1) showed best EL properties with the luminous efficiency of 4.32 cd/A, the power efficiency of 3.98 lm/W and the external quantum efficiency of 2.48% at 500 cd/m2.

Evaluation of anti-microbial activities of ZnO, citric acid and a mixture of both against Propionibacterium acnes.

OBJECTIVE: In this study, anti-microbial activities of ZnO of three different particle sizes of citric acid (CA) and of mixtures of ZnO and CA were confirmed against Propionibacterium acnes. METHODS: ZnO with the smallest particle size showed relatively high anti-microbial activity by disc diffusion assay and broth macrodilution assay. The mixtures of ZnO and CA also showed relatively high anti-microbial activity when the particle size of ZnO was the smallest. Furthermore, anti-microbial activities of ZnO, CA and the mixtures of ZnO and CA were compared through the checkerboard assay. RESULTS: The results indicated that a 1 : 1 ratio of ZnO and CA resulted in the highest anti-microbial activity. The substances were confirmed to have synergic anti-microbial effects. With the time-kill curve assay, the mixture of ZnO-containing CA reduced the surviving microbial content the most after 24 h. CONCLUSION: The results of our study suggest that ZnO may not only be an anti-microbial ingredient for the prevention of and treatment of acne. The results of our study suggest that ZnO may be an anti-microbial ingredient for the prevention of and treatment of acne when mixed with CA.

Physical characterization and in vitro skin permeation of solid lipid nanoparticles for transdermal delivery of quercetin.

OBJECTIVE: Quercetin, a phenolic compound isolated from plants, can act as an antioxidant to protect the skin from oxidative stress induced by ultraviolet rays. The aims of this work were (i) to compare the physical characterization of quercetin-loaded solid lipid nanoparticles (QSLNs) and (ii) to investigate the enhanced skin permeation of quercetin using QSLNs. METHODS: QSLNs were prepared with a certain amount lipid (palmitic acid) and the different ratio of surfactant (Tween(®) 80) by homogenization and ultrasonification method. RESULTS: QSLNs showed mono-dispersed particle size distribution in the ranges of 274.0-986.6 nm and zeta potential from -50.4 to -29.4 mV. Entrapment efficiency of QSLN was 15.2-46.2%, and their crystallinity index was low (0-18.2%). In vitro occlusion test showed QSLN-2 has the highest occlusive effect due to its smallest particle size (274.0 nm), and through these result, QSLN-2 was selected as the optimum formulation. Transmission electron microscopy (TEM) analysis further confirmed the uniform spherical shape of QSLN-2 particles. Field emission-scanning electron microscope (FE-SEM) analysis and histological observation of hairless rat skin showed that the lipid particles of QSLN-2 formed a fused lipid film and, subsequently, it hydrated the surface of the rat skin. Franz diffusion cell was used to measure in vitro skin permeation of quercetin dissolved in propylene glycol (QPG), QSLN-2 and QSLN-3. The results showed that QSLN-2 (33.5 µg cm(-2) , 21.9%) exhibited higher skin permeability than QPG (6.6 µg cm(-2) , 4.2%) and QSLN-3 (14.2 µg cm(-2) , 9.1%), which was visually confirmed by confocal laser scanning microscope (CLSM) image analysis as well. CONCLUSION: The results suggest that QSLN-2, prepared with a surfactant content of 2%, could be used as useful skin delivery system for transdermal delivery of hydrophobic antioxidants such as quercetin.

Preparation and characterization of W/O microemulsion for removal of oily make-up cosmetics.

OBJECTIVE: In the present study, W/O microemulsions (MEs) were prepared for efficient removal of oily make-up cosmetics and the detergency characteristics were studied. METHODS: The W/O MEs were prepared by mixing of a spontaneous emulsifier, cosurfactant and oil, and solubilizing the mixture during addition of water. The wettability and emulsifying activity were, respectively, evaluated by measuring contact angle and absorbance after preparing a total of 20 samples using three emulsifying systems and seven oils. RESULTS: Based on the results, a lower viscosity of the oil component is favourable for higher wettability, and the lower the viscosity of the emulsifying systems, the higher the wettability of the ME. Except in the case of oleic acid (OA), oils having high polarity showed significant emulsifying activity. The equation describing [detergency(ΔE)=98.1wettability(cosθ)+120.5EAI(emulsifyingactivityindex)-77.1] was derived from the detergency measurement results, and it was verified that the wettability contributed more significantly to the detergency than the emulsifying activity. CONCLUSION: These results suggest that the prepared W/O microemulsions can be utilized as cleaning agents for efficient removal of oily make-up cosmetics.

Enhanced skin delivery of liquiritigenin and liquiritin-loaded liposome-in-hydrogel complex system.

OBJECTIVE: To study the permeation of liquiritigenin (LQG) and liquiritin (LQ) as licorice flavonoids into the skin, we prepared ceramide liposome-in-cellulose hydrogel complex system. METHODS: Liposome-in-hydrogel complex systems were developed by incorporating ceramide liposomes into cellulose hydrogels by the swelling method. We evaluated their physical and chemical properties, encapsulation efficiency and skin permeability using Franz Diffusion Cell. It was visually seen by CLSM images analysis. RESULTS: The ceramide liposome, consisting of biocompatible lipid membranes, remained stable for over 3 weeks. Encapsulation efficiencies for liquiritigenin and liquiritin-loaded liposome-in-hydrogel were 69.39% and 64.71%, respectively. Liposome-in-hydrogel complex systems (LQG: 56.55%, LQ: 66.99%) had greater skin permeability than control (LQG: 4.92%, LQ: 5.30%) or a single liposome systems (LQG: 43.34%, LQ: 48.97%) and hydrogel systems (LQG: 38.21%, LQ: 55.07%). CONCLUSION: Liposome-in-hydrogel system can be a potential drug delivery system for topical delivery of antioxidants such as licorice flavonoids to construct antioxidative skin barrier.

Localization of synucleins in the mammalian cochlea.

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, alpha-, beta-, and gamma-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that beta-synuclein is the most abundantly expressed form, followed by gamma- and then alpha-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (alpha- and gamma-synuclein), spiral ganglion (beta-synuclein), inner spiral bundle (gamma-synuclein), and stria vascularis (alpha- > beta-synuclein). Developmentally, gamma-synuclein can be seen in the region of the outer hair cells by E19, while alpha- and beta-synuclein do not clearly appear there until approximately P10. Additional studies in a null-mutant gamma-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, gamma-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined.

Protective effect of oxidative stress in HaCaT keratinocytes expressing E7 oncogene.

In a previous study, we established a stable cell line which constitutively expresses E7 in HaCaT human keratinocyte cell line and identified various relevant factors including oxygen modulators affected by the E7 oncogene. E7-expressing HaCaT cells (HaCaT/E7) appeared to be more resistant to H2O2-induced cell death. Here, we demonstrate how E7 oncogene would modulate oxidative stress-induced cell death. In addition, we verified the increased expression of catalase in the HaCaT/E7 by Western blot analysis. The results suggest that the E7 oncogene would induce higher resistance to ROS-induced cell injury in the E7-infected cells via the upregulation of catalase. To investigate these paradoxical effects of high concentrations of H2O2 (500 microM-1 mM), we examined their effects on receptor mediated apoptosis, cell death via the mitochondrial pathway and modulation of apoptosis related factors. Our results revealed that HaCaT keratinocytes infected with HPV 16 E7 oncogene modulated expressions of catalase, Bcl-xL, IL-18, Fas, Bad, and cytochrome c as well as NF-kappaB, resulting in the resistance to oxidative stress-induced cell death.

Photolysis of the organic UV filter, avobenzone, combined with octyl methoxycinnamate by nano-TiO2 composites.

A protection of the skin from harmful UV rays is important in preventing the skin damage and skin aging when exposed to sunlight. Titanium dioxide composites are used as a UV filter in sunscreen products combined with organic compounds such as butyl methoxydibenzoyl methane (avobenzone) and octyl methoxycinnamate (OMC) to improve the function of the sunscreen. In this study, the photolysis of avobenzone and OMC caused by the photocatalytic TiO2 nano composites (NCs) is investigated. Three different types of oil/water (O/W) sunscreen formulations containing avobenzone and OMC were prepared. Each formulation contained one of three different types of surface modified TiO2 NCs, which were WP-S (small sized hydrophilic TiO2NCs, ~10nm), OP-S (small sized hydrophobic TiO2NCs, ~15nm), and OP-L (large sized hydrophobic TiO2NCs, ~200nm). The physicochemical properties of the NCs were analyzed using biophysical tools. Addition of a different size of TiO2NCs into O/W sunscreen formulations significantly increased the photolysis of OMC. Effect of quercetin on degradation of avobenzone and OMC by the NCs was also studied for all three formulations. Although the OP-S NCs showed the lowest photocatalytic ability and the highest UV blocking capability, the NCs promoted the photolysis of OMC to the greatest extent. These results can be utilized to design more effective sunscreens, which could potentially ensure optimal photo-protection.

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18.

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.

Analysis of the conformational change of recombinant human papilloma virus type 18 E7 protein induced by metal binding.

Human papillomavirus (HPV) type 18 E7 gene was isolated by polymerase chain reaction (PCR) amplification from tissues of Korean cervical cancer patients and cloned into a plasmid vector, pET-3a, for the expression of recombinant E7 protein (rE7) in Escherichia coli. The rE7 protein was purified to the homogeneity and its purity was confirmed by HPLC. The purified protein was analyzed for the metal-binding properties by UV spectroscopy and it was shown that two Cd2+ or Zn2+ ions bind to one E7 protein by the metal-sulfur ligand formation via two Cys-X-X-Cys motifs in E7 protein. When the change of intrinsic fluorescence of tryptophan residue was analyzed for rE7-Zn complex, the blue shift of emission wavelength and the decrease in maximum intensity of emission were observed compared with rE7. These results suggest that Zn(2+)-bound rE7 has undergone conformational change, in which a tryptophan residue located in the second Cys-X-X-Cys motif was moved into solvent-inaccessible or hydrophobic environment. The rE7-Zn complex was found to be resistant to chymotrypic digestion by comparing the digestion patterns of rE7. Therefore, we showed the folding status of HPV 18 E7 could be changed by metal binding resulting in a different conformation in which a tryptophan residue was driven into more hydrophobic environment and the resistancy to chymotryptic digestion was conferred.

Synthetic peptides of human papillomavirus type 18 E6 harboring HLA-A2.1 motif can induce peptide-specific cytotoxic T-cells from peripheral blood mononuclear cells of healthy donors.

To identify cytotoxic T-cell (CTL) epitopes against human papillomavirus type 18 (HPV 18) E6 protein that might be useful for developing peptide-based vaccine against HPV 18 infection, 18 peptides which possibly contain CTL epitopes were selected on the basis of previously described human leukocyte antigen (HLA)-A2.1-binding motif and chemically synthesized. In the binding assay of the synthetic peptides, 8 out of 18 synthetic peptides enhanced the expression of HLA-A2.1 molecules on T2 cell surface, which implies that these peptides were able to bind the HLA molecules. Those peptides having good binding affinity to HLA-A2.1 were tested for their ability to activate CTLs which were isolated from peripheral blood mononuclear cells (PBMCs) of healthy blood donors and to kill the target T2 cells pulsed with the same peptide. Five out of eight tested peptides activated CTLs and killed the target cells.

Improvement of gene transfer to cervical cancer cell lines using non-viral agents.

Virus-like particles (VLPs) composed of recombinant capsid protein L1 and L2 of human papillomavirus type 16 were conjugated with polylysine (PL) and gene transfer was performed using VLP-PL conjugates to allow the expression of targeted gene. When HeLa cells were incubated with VLP-PL conjugate coupled with plasmid cytomegalovirus beta-galactosidase (pCMVbeta-gal), about 10% of cells were transfected and demonstrated beta-galactosidase activity. Hence chloramphenicol acetyltransferase activity was also expressed significantly in VLP-PL-plasmid simian virus 2 chloramphenicol acetyl transferase (pSV2CAT)-transfected cells, VLP-PL conjugate was tested whether it could transfer a tumor suppressor gene, pCMVp53, to HeLa cells and the exogenously provided p53 gene complexed to VLP-PL conjugate was detected from HeLa cells by polymerase chain reaction (PCR) analysis. Interestingly, additional increase of transfection efficiency was demonstrated in the presence of poloxamer 407 when C-33A cells were transfected with VLP-PL-pCMVbeta-gal complex. The result support the notion that VLP-PL conjugate may be a promising vector to transfer genetic materials into cancer cells and poloxamer 407 can be used for enhancing the transfection efficiency of VLP-PL conjugate.

Platelet derived growth factor releasing chitosan sponge for periodontal bone regeneration.

With an aim of improving bone regeneration, chitosan sponge containing platelet-derived growth factor-BB (PDGF-BB) were developed. For fabrication of chitosan sponge, chitosan solution was freeze-dried, crosslinked and freeze-dried again. PDGF-BB was incorporated into the chitosan sponge by soaking chitosan sponge into the PDGF-BB solution. Release kinetics of PDGF-BB, cell attachment, proliferation capacity and bony regenerative potentials of PDGF-BB-loaded chitosan sponge were investigated. Prepared chitosan sponge retained porous structure with 100 microm pore diameter that was suitable for cellular migration and growth. Release rate of PDGF-BB could be controlled by varying initial loading content of PDGF-BB to obtain optimal therapeutic efficacy. PDGF-BB-loaded chitosan sponge induced significantly high cell attachment and proliferation level, which indicated good cellular adaptability. PDGF-BB-loaded chitosan sponge demonstrated marked increase in new bone formation and rapid calcification. Degradation of the chitosan sponge was proceeded at defect site and subsequently replaced with new bone. Histomorphometric analysis confirmed that PDGF-BB-loaded chitosan sponge significantly induced new bone formation. These results suggested that chitosan sponge and PDGF-BB-loaded chitosan sponge may be beneficial to enhance periodontal bone regeneration.

3'UTR polymorphisms in the NRAMP1 gene are associated with susceptibility to tuberculosis in Koreans.

SETTING: Korea University and the Korean Institute of Tuberculosis, Seoul, Korea. OBJECTIVE: To determine whether polymorphisms in the 3' untranslated region (UTR) of the NRAMP1 gene are associated with susceptibility to tuberculosis in Koreans. DESIGN: A case-control study design was used to compare the frequency of 3'UTR of NRAMP1 among 192 tuberculosis patients and 192 healthy individuals. All of the samples were diagnosed by X-ray, smear and culture tests between 1998 and 1999 in the Cross of Lorraine Clinic at the Korean Institute of Tuberculosis. RESULTS: A significant association was found between the Korean tuberculosis patients and polymorphisms in the 3'UTR of the NRAMP1 gene (odds ratio [OR] 1.845; 95% confidence interval [CI] 1.097-3.104; chi2 = 5.424; P = 0.020). CONCLUSION: This study showed that genetic variations in the human NRAMP1 gene are associated with susceptibility to smear-positive tuberculosis in Korean patients. The 3'UTR variant allele associated with susceptibility to tuberculosis is very uncommon in Caucasians, but is present in Koreans and West Africans. These observations may explain in part why African Americans and Koreans have greater susceptibility to tuberculosis than Caucasians.

Implication of adenosine A2A receptors in hypotension-induced vasodilation and cerebral blood flow autoregulation in rat pial arteries.

This study aimed to evaluate the role for adenosine A2A receptors in the autoregulatory vasodilation to hypotension in relation with cerebral blood flow (CBF) autoregulation in rat pial arteries. Changes in pial artery diameters were observed directly through a closed cranial window. Vasodilation induced by adenosine was markedly suppressed by ZM 241385 (1 micromol/l, A2A antagonist) and alloxazine (1 micromol/l, A2B antagonist), but not by 8-cyclopentyltheophylline (CPT, 1 micromol/l, A1 antagonist). CGS-21680-induced vasodilation was more strongly inhibited by ZM 241385 (25.3-fold; P<0.05) than by alloxazine. In contrast, 5'-N-ethylcarboxamido-adenosine (NECA)-induced vasodilation was more prominently suppressed by alloxazine (12.0-fold; P<0.001) than by ZM 241385. The autoregulatory vasodilation in response to acute hypotension of the pial arteries was significantly suppressed by ZM 241385, but not by CPT and alloxazine. Consistent with this finding, the lower limit of CBF autoregulation significantly shifted to a higher blood pressure by 1 micromol/l of ZM 241385 (53.0+/-3.9 mm Hg to 69.2+/-2.9 mm Hg, P<0.01) and 10 micromol/l of glibenclamide (54.7+/-6.5 mm Hg to 77.9+/-4.2 mm Hg, P<0.001), but not by CPT and alloxazine. Thus, it is suggested that adenosine-induced vasodilation of the rat pial artery is mediated via activation of adenosine A2A and A2B receptors, but not by A1 subtype, and activation of adenosine A2A receptor preferentially contributes to the autoregulatory vasodilation via activation of ATP-sensitive K+ channels in response to hypotension and maintenance of CBF autoregulation.

Different distribution of HLA class II alleles according to response to corticosteroid therapy in sudden sensorineural hearing loss.

OBJECTIVE: To investigate the association of HLA class II alleles with the susceptibility to sudden sensorineural hearing loss and with the results of corticosteroid treatment in the Korean population. DESIGN: HLA-DRB1, -DQA1, -DQB1, and -DPB1 genotyping by the sequence-specific oligonucleotide probes method in 41 patients with sudden sensorineural hearing loss and in 206 healthy control subjects. Initial hearing levels at the onset of hearing loss and final hearing levels after treatment were evaluated for the association with HLA class II alleles. SETTING: Tertiary care referral center, ambulatory and hospitalized care. SUBJECTS: Forty-one patients (24 men and 17 women; mean age, 49.2 years) were compared with 206 controls. Patients were divided into 2 groups according to their response to corticosteroid therapy (good response vs nonresponse). RESULTS: The frequencies of HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles were not significantly different between patients and controls (P>.05). When an association between the results of corticosteroid treatment and the frequency of HLA alleles was evaluated, the frequencies of HLA-DRB1*14 (relative risk [RR] = 3.5, P<.02), -DQA1*03 (RR = 4.2, P<.02), and -DQA1*05 (RR = 3.1, P<.03) were significantly increased, but HLA-DQA1*01 (RR = 0.2, P<.004) and -DQB1*06 (RR = 0.2, P<.009) were decreased in the group nonresponsive to corticosteroid therapy, compared with the controls. The distribution of HLA-DQA1*01 (P<.04), -DQB1*06 (P<.02), and -DQA1*03 (P<.003) was significantly different between the responsive and the nonresponsive groups. HLA-DQA1 allelic combination analysis showed that the frequencies of DQA1*03 and *05 had a high RR value in patients with sudden sensorineural hearing loss (RR = 4.1, P<.003) and in patients in the nonresponsive group (RR = 8.9, P<.001), compared with the controls. CONCLUSION: The presence of HLA class II alleles may be a useful genetic marker in forecasting a prognosis in Korean patients with sudden sensorineural hearing loss.

The antibody response to HPV proteins and the genomic state of HPVs in patients with cervical cancer.

Human papillomavirus (HPV) DNAs are often found to be integrated into the human genome in high-grade cervical intraepithelial neoplasia (CIN) as well as in invasive cervical cancers. Investigation of the relationship between the genomic status of specific HPV genes and their antibody responses to the virus-like particles (VLPs) of HPV-16 L1/L2 proteins and the in vitro translated HPV-16 E6 and E7 proteins may help to illustrate the mechanism of HPV-related cervical carcinogenesis and host immune response. Cervical cancer tissues obtained from 39 patients were studied to evaluate the physical status of HPV genes by Southern blotting, DNA-PCR, and RT-PCR of E2. The antibody response against the HPV-16 L1/L2 VLPs of serum specimens were tested by ELISA and the antibody response against the HPV-16 E6 and E7 proteins were tested by radioimmunoprecipitation assay (RIPA), respectively. Integrated forms of HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervical cancer patients showed a significantly higher prevalence rate (39.5%; 15/38) of antibodies to HPV-16 L1/L2 VLPs than that of the control group (8.7%; 2/28) (P < 0.05). Antibodies to HPV-16 L1/L2 VLPs were more commonly detectable in cervical cancer patients having the episomal form of HPV-16 DNA (pure episomal and mixed forms) (60%; 9/15) than in those who had only the integrated forms of HPV-16 DNA (26.1%; 6/23) (P < 0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer, respectively. These were significantly higher than the positive rates for the control group (8.3% and 2.8%) (P < 0.05). The differences between sero-reactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA and those with integrated forms of HPV-16 DNA were not statistically significant (P > 0.05). Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer in Korea. Antibodies to HPV-16 L1/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins, appeared in a significantly larger proportion of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 L1/L2 VLPs were more often detected in cervical cancer patients having the episomal form of HPV-16 DNA than in those having only integrated forms of HPV-16 DNA. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states.

Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice.

The effects of two ginseng saponins having a different ratio of protopanaxadiol (PD) and protopanaxatriol saponins (PT) on the learning impairment induced by scopolamine, and learning and memory in mice were investigated in a passive avoidance task and a Morris water maze task. The ratio of PD and PT was 1.24 and 1.46, respectively. Before training, the ginseng saponins were administered intraperitoneally at doses of 50 and 100 mg/kg. The two saponins improved the scopolamine-induced learning impairment at different dosages in mice, 50 and 100 mg/kg, respectively. However, the two saponins did not show a favorable effect on learning and memory in normal mice. Korean red ginseng saponin with a low PD/PT ratio had an improving effect on spatial working memory, but the saponin with a high PD/PT ratio did not. This finding suggests that the PD/PT ratio of the ginseng saponins may be an important factor in the pharmacological role of red ginseng as a medicinal herb.