The change of etiological agents and clinical signs of epidemic viral conjunctivitis over an 18-year period in southern Taiwan

BACKGROUND: Epidemic viral conjunctivitis is a highly contagious eye disease that occurs worldwide and is caused mainly by adenoviruses and enteroviruses. An 18-year analysis of the changes of pathogens and clinical signs in a subtropical and densely populated island presents certain special features. METHODS: We retrospectively analyzed the clinical information and laboratory records of the conjunctivitis patients with positive conjunctival swabs from 1980 to 1997. RESULTS: The positive rate of laboratory diagnosis of epidemic conjunctivitis was 50.0% (1,233/2,467). From 1980 to 1994, the predominant causative agent of adenoviral keratoconjunctivitis was adenovirus type 8 (Ad8), with six genotypes being evolved. Three of the new Ad8 genotypes each caused a new epidemic. After 1995 the predominant adenoviral pathogens shifted to Ad37 and Ad19, and no more Ad8 was isolated. Enterovirus type 70 (EV70) was isolated from four outbreaks of acute hemorrhagic conjunctivitis (AHC) from 1980 to 1984, but rarely in later years. Coxsackievirus A type 24 variant (CA24v), which first appeared in 1985, appeared later as the causes of four major epidemics of AHC from 1985 to 1994. The overall clinical symptoms of viral conjunctivitis were more severe in the 1990s than in the 1980s. CONCLUSION: In southern Taiwan, outbreaks of adenoviral keratoconjunctivitis caused by new genomic variants could be associated with the long-term endemic co-circulation of Ad8, Ad19, and Ad37, while epidemics of CA24v AHC were caused mainly by introduction of new viral strains from neighboring countries. The aggravation of host symptoms in the 1990s needs further investigation and close follow-up.     

Noninvasive Characterization of Regional Variation in Drug Transport into Human Stratum Corneum in Vivo

Purpose. To investigate the mechanisms underlying the regional variations in drug transport into human stratum corneum (SC) of two model compounds of different lipophilicity and molecular size, 4-cyanophenol (CP) and cimetidine (CM), in vivo by non-invasive, quantitative attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Methods. Saturated solutions of CP and CM were applied to the skin surface of eleven Chinese men, at five anatomical sites, including forearm, back, thigh, leg, and abdomen, for 10-15 min and 3-5 h, respectively. After the skin surface was cleansed of remaining chemicals, the SC was tape-stripped sequentially up to 20 times, and the drug concentration profiles in the tape-stripped SC were determined using ATR-FTIR spectroscopy. Thickness of the SC was estimated simultaneously using two-point measurements of transepidermal water loss before and after completion of tape stripping. Estimation of partition, diffusion, and permeability coefficients was achieved by analysis of the data using the unsteady-state diffusion equation. Results. The rank orders of regional variation in partition and diffusion coefficients of CP and CM were different. The rank order of regional variation in permeability coefficients was similar for both drugs and decreased in the order of back > forearm > thigh > leg abdomen, but the variation was more prominent for CM. Conclusions. Regional variation in SC transport of CP was mainly influenced by its intrinsic diffusivity across the SC, whereas variation in transport of CM could be attributed to both thermodynamic and kinetic differences among different anatomical skin sites.     

Junceol A, a new sesquiterpenoid from the sea pen Virgularia juncea

A new sesquiterpenoid, junceol A(1), as well as two known diterpenoids, sclerophytin A (2) and cladiellisin (3), have been isolated from the sea pen octocoral Virgularia juncea. The structure of metabolite 1 was determined by extensive spectral analysis. Compounds 1-3 have been shown to exhibit cytotoxicity toward P-388 cancer cells.     

A novel role of metalloproteinase in cancer-mediated immunosuppression

Depressed immune responses have been observed frequently in cancer patients. In a variety of human malignancies, the expression of interleukin-2 receptor alpha (IL-2R alpha) on activated tumor-infiltrating lymphocytes was down-regulated. Because IL-2R alpha plays a pivotal role in the development and propagation of functional T cells, its depressed expression may result in poor function of tumor-reactive cytotoxic lymphocytes. For elucidating the mechanism responsible for down-regulation of IL-2R alpha, a coculture model of in vitro mixed autologous lymphocytes and tumor cells was established. Kinetic analysis showed that cervical cancer cells down-regulated IL-2R alpha expression on encountered T cells. The amount of IL-2R alpha mRNA in tumor-infiltrating lymphocytes-derived CD8+ T cells was compatible with that in the corresponding activated CD8+ T cells. Additional evidence showed that cervical cancer cells could induce the release of soluble IL-2R alpha expression on encountered T cells. By using protease inhibition assays we demonstrated that tissue inhibitors of metalloproteinase abrogated the cancer-mediated IL-2R alpha proteolytic process and restored the T-cell proliferation function. Immunohistochemical stainings further revealed prominent metalloproteinase (MMP) expressions, including MMP-1, MMP-2, and MMP-9, in cervical cancer tissues. Additional in vitro studies showed that MMP-9 mediates cleavage of IL-2R alpha and down-regulates the proliferative capability of cancer-encountered T cells. Our findings suggest a new role of MMPs in tumor-mediated immunosuppression and provide a possible therapeutic potential for patients with cervical cancer.     

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed, although less than 10% of female lung cancer patients are smokers. Until now, the etiological factor remains unknown. We hypothesize that high-risk human papillomavirus (HPV) 16/18 may be associated with lung cancer development based on high prevalence of p53 negative immunostainings in female lung tumors compared with that of male lung tumors. In this study, 141 lung cancer patients and 60 noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH), respectively. The concordant detection of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of 141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18 infection of nonsmoking female lung cancer patients is much higher at 10.12 (95% confidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval, 0.84-4.76) of nonsmoking male lung cancer patients. This result strongly suggests that HPV infection is associated with lung cancer development of nonsmoking female lung cancer patients. The high prevalence of HPV 16/18 infection may explain to a certain extent why Taiwanese women nonsmokers had a higher lung cancer mortality rate.     

Bilateral anomalous origins of the posterior meningeal artery from the ascending pharyngeal arteries

We present a rare case of angiographically confirmed dural arteriovenous fistula supplied mainly by the posterior meningeal artery with bilateral anomalous origins from the bilateral ascending pharyngeal arteries. The bilaterality of the origins of the posterior meningeal artery is important in the angiographic diagnosis and management of a dural vascular malformation in the posterior fossa or the posterior part of the falx cerebri.     

Development and validation of a WHOQOL-BREF Taiwanese audio player-assisted interview version for the elderly who use a spoken dialect

A quality of life questionnaire is rarely adapted to an interview mode for people who mainly use spoken language in daily life. In Taiwan, the WHOQOL-BREF (Mandarin Chinese version) has been developed, as a self-administered questionnaire, but it cannot be applied to the majority of the elderly in Taiwan, who speak only Taiwanese (a dialect). This study adopted the audio player-assisted interview mode to develop a Taiwanese version of the WHOQOL-BREF specifically for Taiwanese-speaking elderly people, and followed with examinations of the reliability and validity of this version. Initially, the WHOQOL-BREF (English version) was translated into colloquial Taiwanese, and field tests confirmed the equivalence and appropriateness of the translation. A total of 228 Taiwanese-speaking elderly people were assessed using the Taiwanese interview version, of which 144 subjects were re-assessed two weeks later. Interviewers assessed each subject aided by an audio player on which all the translated WHOQOL-BREF contents were recorded. The Taiwanese interview version of the WHOQOL-BREF, except for the item related to dependence on medication, showed acceptable reliability (internal consistency, corrected item-domain correlation, and test–retest reliability) and validity (criterion-related, convergent, and discriminant validity). Confirmatory factor analyses supported the four-factor model of the Taiwanese interview version, providing evidence for construct validity. The results suggest that the Taiwanese audio player-assisted interview version of the WHOQOL-BREF was reliable and valid in assessing quality of life of elderly Taiwanese.     

Structures and cytotoxicity relationship of isoaaptamine and aaptamine derivatives.

A series of 9-O-acylisoaaptamine (3-14) and 4-N-acyl-dihydroaaptamine (16-19) derivatives have been prepared and evaluated for antitumor activity against murine P-388 and human tumor cells including KB16, A549, and HT-29 cell lines. All of compounds showed significant cytotoxicity against P-388 cells. Among them, compounds 9-11 showed potent activity as isoaaptamine (1). There was an apparent lack of linear relationship between cytotoxicity and carbon number of the side chain. The structure and activity relationship for these particular compounds are discussed.