Risk of systemic lupus erythematosus in patients with human papillomavirus infection: a population-based retrospective cohort study.

BACKGROUND: Viral infection contributing to systemic lupus erythematosus (SLE) development has been largely reported. However, the SLE risk in patients with human papillomavirus (HPV) infection is unknown. METHODS: Data were retrieved from the Longitudinal Health Insurance Database (2000) in Taiwan. We identified 43,567 patients with HPV infection and 174,268 age- and sex-matched uninfected controls from 2002 to 2012. Individuals were followed up from index date (first date of diagnosis with HPV) until the occurrence of SLE, at the end of the study (December 2013), or when they were withdrawn from the insurance program. The incidence rate ratio (IRR) was calculated using the univariate Poisson regression. The adjusted hazard ratios (aHRs) were calculated, and sensitive and subgroups analyses were also conducted. RESULTS: Compared with the non-HPV controls, the IRR of SLE in HPV patients was 1.52 (95% confidence interval (CI): 1.09-2.12). The risk of SLE in HPV-infected individuals was significantly high (aHR: 1.48, 95% CI: 1.06-2.06) after adjusting for age, sex, and comorbidities. Men aged between 16 and 45 years were more susceptible to developing SLE (aHR: 21.57, 95% CI: 2.52-184.60, p = 0.0051). CONCLUSION: Our study showed a significantly higher risk of SLE among HPV-infected patients, especially in men aged between 16 and 45 years.

Cataract risk of neuro-interventional procedures: a nationwide population-based matched-cohort study.

AIM: To demonstrate the risk of cataract associated with radiation exposure from neuro-interventional procedures. MATERIALS AND METHODS: This was a nationwide population-based, matched-cohort study. The exposed group (group E) comprised patients diagnosed with an aneurysm, cerebrovascular system anomaly, or subarachnoid haemorrhage who underwent a neuro-interventional procedure, such as brain digital subtraction angiography or endovascular embolisation. The comparison group (group C) included subjects who were never exposed to radiation from neuro-interventional procedures and were propensity score-matched by the date of enrolment, age, sex, and associated comorbidities. Multiple Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) of cataract risk due to radiation exposure while adjusting for potential confounding factors. RESULTS: There were 838 patients and 3,352 matched subjects in groups E and C, respectively. The incidence of cataracts was significantly greater among subjects in group E (adjusted HR [aHR] = 1.88; 95% confidence interval [CI] = 1.08-3.26), especially those aged >40 years (aHR = 2.14; 95% CI = 1.16-3.94). The number of computed tomography examinations was positively correlated, but not statistically significant, with an increased risk of cataract occurrence. CONCLUSIONS: Neuro-interventional procedures might be significantly associated with an increased risk of cataract occurrence.

Traditional Chinese medicine use may reduce medical utility in patients with asthma: a nationwide population-based retrospective cohort study.

BACKGROUND: Many patients with atopic diseases, including asthma, have sought complementary and alternative medicine and traditional Chinese medicine (TCM) treatments. But, limited clinical studies have yet examined TCM effects on medical utility in asthma patients. AIM: To assess the medical utility of TCM in patients with asthma. DESIGN: Population-based retrospective cohort study. METHODS: We performed a 13-year population-based retrospective cohort study. A total of 5235 asthma patients who were TCM users and 5235 propensity-score matched asthma patients who never used TCM were sampled from the Taiwan National Health Insurance Research Database from 2000 to 2012. We compared these two groups of patients to calculate their medical utility, including numbers of emergency visits and hospitalizations until 2013. Univariate analyses were performed using Chi-square tests for dichotomous variables and t-tests for continuous variables. Cox proportional hazard models were conducted to investigate the medical utility of asthma after TCM use. RESULTS: Compared with non-TCM patients, TCM patients had a significantly decreased medical utility of asthma admission [adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI): 0.46-0.85; P < 0.05], especially in patients who used TCM for >60 days. Asthma medical utility in asthma emergencies was significantly higher for male than for female patients (adjusted OR = 1.45; 95% CI: 1.08-1.96). The most frequently used TCMs for asthma control or cough treatment were antitussive agents. CONCLUSION: This population-based retrospective cohort study showed a significantly decreased medical utility of emergency visits and admissions in TCM patients, especially using TCM for >60 days.

Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome.

OBJECTIVES: To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). METHODS: This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. RESULTS: Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). CONCLUSIONS: HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.

Molecular characterization of a defensin gene from the mosquito, Aedes aegypti.

Insect immune proteins, defensins, are inducible anti-Gram-positive bacterial peptides. We report here the identification of two defensin genes from the mosquito, Aedes aegypti, which encode a large 541 bp transcript (AaDef Ala) and a small 473 bp transcript (AaDef Asm). The cDNA corresponding to AaDef Ala was cloned, sequenced, and compared with the previously reported AaDef Asm cDNA. The AaDef Ala gene was isolated through genomic library screening and characterized. It putative regulatory region contains a 64 bp intron, a TATA box and a putative arthropod initiator. Two 150 bp long direct and several palindromic repeats are present in this sequence. Similar to other insect immune peptide genes, the AaDef Ala gene contains numerous putative regulatory motifs with impressive similarity to elements of vertebrate acute phase response protein genes.

Plasma proteomic profiling for detecting and differentiating in situ and invasive carcinomas of the uterine cervix.

The objective of this study was to identify multiple plasma protein markers that might be characteristic of in situ and invasive cervical cancers. Plasma samples obtained from patients with in situ cervical cancer (carcinoma in situ [CIS], n= 32), from patients with early invasive cervical cancer without lymph node metastasis (squamous cell carcinoma [SCC], n= 60), and from age-matched disease-free controls (n= 37) were analyzed by cation-exchange protein chips and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry. A classification tree defined by six protein peaks could discriminate 84 of the 92 cancers (CIS and SCC) and 36 of the 37 controls, with 91% sensitivity and 97% specificity. In comparing the CIS and SCC samples, two protein peaks with Mr values of 6586.41 and 3805.68 were able to classify 55 of the 60 SCC and 31 of the 32 CIS samples, with 92% sensitivity and 97% specificity. This study demonstrates for the first time the feasibility of differentiating in situ and invasive cervical cancers through plasma protein profiling. Identification of the proteins different in invasive and in situ cancer may be of great value in the understanding of cervical cancer invasion and in the development of novel therapeutic intervention.

Plasma proteomic pattern as biomarkers for ovarian cancer.

Early detection of ovarian cancer remains a challenge. Pathologic changes within an organ might be reflected in proteomic patterns in serum or plasma. The objective of this study was to identify new plasma biomarkers in ovarian cancer patients using mass spectrometry (MS) protein profiling and artificial intelligence. The study included 35 women with ovarian cancer and 30 age-matched disease-free controls. For plasma protein signature analysis, the protein chip array surface-enhanced laser desorption/ionization (SELDI) analysis was performed. The strong anion exchange (SAX) and weak cation exchange (WCX) chips were used for analysis. After a training analysis by SAX and WCX protein chips, learning algorithm and clustering analysis was performed to reach a discriminate pattern of protein signature. SELDI mass spectroscopy was highly reproducible in detecting ovarian tumor-specific protein profiles. Four specific protein peaks were identified in plasma of women with ovarian cancer, but not in controls, with relative molecular masses of 6190.48, 5147.06, 11522.6, and 11537.7 d. Two peaks, with Mr 5295.5 and 8780.48 d, were present in plasma of control but not in women with ovarian cancer. A sensitivity of 90-96.3% and specificity of 100% for this studied cases and controls were reached. This study clearly demonstrates that the combined technology of SELDI-MS and artificial intelligence is effective in distinguishing protein expression between normal and ovary cancer plasma. The identified gained and lost protein peaks in plasma may provide as candidate proteins to be used for the detection or monitoring ovarian cancer.

Okadaic acid, a protein phosphatase inhibitor, inhibits nerve growth factor-directed neurite outgrowth in PC12 cells.

The biochemical mechanisms involved in neurite outgrowth in response to nerve growth factor (NGF) have yet to be completely resolved. Several recent studies have demonstrated that protein kinase activity plays a critical role in neurite outgrowth. However, little information exists about the role of protein phosphatases in the process. In the present study, okadaic acid, a phosphatase inhibitor (specific for types 2A and 1) and tumor promoter, was used to investigate the role of protein phosphatases in neurite outgrowth in PC12 cells. PC12 cells cultured in the presence of 50 ng/ml of NGF started to extend neurites after 1 day. After 3 days, 20-25% of the cells had neurites. Okadaic acid inhibited the rate of neurite outgrowth elicited by NGF with an IC50 of approximately 7 nM. This inhibition was rapidly reversed after washout of okadaic acid. Okadaic acid also enhanced the neurite degeneration of NGF-primed PC12 cells, indicating that continual phosphatase activity is required to maintain neurites. Taken together, these results reveal the presence of an okadaic acid-sensitive pathway in neurite outgrowth and imply that protein phosphatase plays a positive role in regulating the neuritogenic effects of NGE.

[Clinical experience of infantile hypertrophic pyloric stenosis].

Infantile hypertrophic pyloric stenosis (IHPS) is a relatively common disease. We report our experience with 24 IHPS infants admitted to the Departments of Pediatrics and Pediatric Surgery of Chang Gung Memorial Hospital in Kaohsiung over 4 years, from 1986 to 1989. Analysis disclosed a high male to female ratio (11:1) and a heavy preponderance of firstborn male (46%). Fifty per cent of our cases had symptoms beginning between the ages of 2-4 weeks. The fact that 67% of the patients had duration of symptoms longer than 2 weeks prior to admission, with a mean interval of 25 days of progressive symptoms, represented that there was delay in diagnosis and treatment in most of our cases. The major clinical manifestations were projectile vomiting (100%), palpable pyloric mass (66.7%) and visible gastric peristaltic waves (41.7%). Of the 18 cases receiving plain supine abdominal roentgenogram, 17 (94.4%) demonstrated typical pictures. A gastric air outline extending below L2 vertebra is the most helpful criteria. Preoperative sonography suggested that the determination of pyloric muscle wall thickness predicted IHPS more accurately than that of pyloric muscle length. All 24 cases received Fredet-Ramstedt pyloromyotomy, with no mortality and short hospitalizations.

A novel mutation in the hepatocyte nuclear factor-1alpha/MODY3 gene in Chinese subjects with early-onset Type 2 diabetes mellitus in Taiwan.

AIMS: The goal of this study was to determine the frequency of mutation in hepatic nuclear factor (HNF)-1alpha, a gene recently implicated as causing maturity-onset diabetes of the young (MODY) and to analyse the respective clinical presentations in an ethnically Chinese population. METHODS: Fifteen unrelated subjects (nine females and six males) aged less than 35 years who had early-onset diabetes were analysed to test the possibility that mutation of the HNF-1alpha gene was responsible for this disorder. Genomic DNA extraction, polymerase chain reaction and DNA sequence analysis were performed accordingly. RESULTS: One patient with MODY had a novel missense mutation in exon 3 of the HNF-1alpha gene (Y218C) in a region of the protein that corresponds to a predicted DNA binding domain. CONCLUSIONS: A Y218C mutation in HNF-1alpha gene was identified in one family in Taiwan.

Regulation of adenylyl cyclase type VI activity during desensitization of the A2a adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A.

We reported earlier that inhibition of adenylyl cyclase activity is a mechanism involved in desensitization of the A2a adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC-12 cells. Here, we investigated the molecular mechanism that modulates adenylyl cyclase activity during A2a desensitization. Reversible inhibition of forskolin-evoked adenylyl cyclase activity in desensitized cells occurred after incubation with an A2a-selective adenosine agonist (CGS21680). However, when okadaic acid (a relatively protein phosphatase 2A-specific phosphatase inhibitor) was added after agonist removal, adenylyl cyclase activity did not recover. Okadaic acid caused significant dose-dependent inhibition of adenylyl cyclase activity in intact PC-12 cells. Prolonged exposure of okadaic acid-treated PC-12 cells to adenosine agonists did not evoke further inhibition, suggesting that the inhibition of adenylyl cyclase activity during A2a desensitization may operate through a pathway that overlaps with the increased phosphorylation caused by okadaic acid. Inclusion of calcium in the adenylyl cyclase assay significantly inhibited cyclase activity. indicating that PC-12 cells contain Ca(2+)-inhibitable type VI adenylyl cyclase (AC6). This was confirmed by polymerase chain reaction-based detection of AC6 cDNA. Furthermore, incubation of PC-12 cell membrane fractions with purified protein phosphatase 2A or coexpression of protein phosphatase 2A with AC6 in COS-1 cells significantly increased AC6 activity. To reduce the possible influence of Gs alpha protein, we substituted guanosine-5'-O-(2-thio)diphosphate and MnCl2 for GTP and MgCl2, respectively, in some cyclase assays and found that the suppression of AC6 during A2a desensitization and okadaic acid treatment remained largely unchanged. Taken together, these data suggest that phosphorylation of AC6 might account for the inhibition of adenylyl cyclase activity during A2a desensitization in PC-12 cells.

Identification of immune-related protein kinases from mosquitoes (Aedes aegypti).

Protein kinases are known to be involved in signal transduction for numerous physiological events. However, little is known about the roles of protein kinases in insect immunity. A fragment around 150 bp was amplified by polymerase chain reaction using cDNA templates from bacterial inoculated mosquitoes and primers corresponding to the conserved domain of protein kinases. Based on sequence analysis, 11 groups of protein kinases were characterized including 3 nonreceptor tyrosine kinases, 3 receptor tyrosine kinases, 3 serine/threonine kinases, and 2 novel protein kinases. The most abundant kinase obtained in this study reveals a high degree of similarity to human cholinesterase-related cell division controller (CHED) protein kinase. The expression of this mosquito CHED-like kinase is not detectable in normal female mosquitoes, but induced only after bacterial inoculation and trauma. A mosquito protein kinase was demonstrated to share homology with a plant Tousled gene, but has not yet been characterized in the animal system. In addition, analysis of the sequences of several protein kinases cloned from mosquitoes suggests that they might be involved in the regulation of cellular or humoral immunity.

Purification and characterization of a novel phospholipase A2 from king cobra (Ophiophagus hannah) venom.

A novel phospholipase A2, designated as Oh-DE-2, was isolated from the venom of Ophiophagus hannah (king cobra) by successive chromatography on SP-Sephadex C-25, DE-52, and Q-Sepharose columns. Oh-DE-2 with pI 5.1 showed an apparent molecular weight of 14 kD as revealed by SDS-PAGE and gel filtration. The amino acid sequence was homologous with those of PLA2S from Elapidae venoms. Oh-DE-2 was effectively inactivated by p-bromophenacyl bromide, indicating that the conserved His-48 is essential for its enzymatic activity. However, modification of the conserved Trp-19 did not cause a precipitous drop in the enzymatic activity of Oh-DE-2 as observed with PLA2S from Naja naja atra and Bungarus multicinctus venoms. A quenching study showed that the microenvironment of Trp in Oh-DE-2 was inaccessible to acrylamide, iodide, or cesium, a finding which was different from those observed with PLA2S from N. naja atra and B. multicinctus venoms. These results might suggest that, unlike other PLA2 enzymes, Trp-19 in Oh-DE-2 is not directly involved in its enzymatic mechanisms.

[Cephalosporin C production by solid state fermentation with rice grains].

The purpose of the present study was to investigate the production of cephalosporin C in solid state fermentation with rice as a basal substrate. Among the various grains as basal substrates tested, rice was the best one and the worst one was soyflour . Among the varieties of rice examined, Tsailai rice was the best. The proposed best formula for the fermentation medium on the basis of 10 g rice grain consists the following % of the ingredients, 0.65, peptone, 0.65, ammonium sulfate, 0.26, inositol, 1.3 (v/w), trace element solution, 0.65 calcium carbonate, 0.65 calcium sulfate, 0.065, potasium sulfate, 1.3, sucrose, 0.13, DL-methionine and 2.6, methyl oleate. Of the strains of C. acremonium used, strain M8650 -R-3 was superior to strain ATCC 14553. The optimum inoculum density was 2.8 X 10(8) spores of C. acremonium M8650 -R-3 per g substrate. The initial moisture content of the medium at 49-51%, the water activity at 0.985, and the fermentation temperature at 25 degrees C were found as the optimun . After 7 days of fermentation, the maximum yield of cephalosporin C was 6420 micrograms per g substrate and the total cephalosporin C equivalent potency was 11,000 micrograms per g substrate.

[Identification of Staphylococcus epidermidis by desferrioxamine susceptibility and trehalose fermentation tests].

The importance of coagulase-negative staphylococci, especially Staphylococcus epidermidis in clinical and nosocomial infection are recognized increasingly in recent years. A rapid and accurate identification of S. epidermidis is therefore important and necessary. A new test, susceptibility to desferrioxamine, coupled with trehalose fermentation has been recommended for the identification of this organism. However, the medium and method used are different from what has been recommended by the NCCLS. To investigate the feasibility of using the desferrioxamine susceptibility test in conjunction with the routinely used disc agar diffusion test, we employed 111 staphylococcal strains (including 51 S. epidermidis isolates, 15 S. hominis and 45 other coagulase-negative staphylococci) as test organisms, and followed the procedures recommended by the NCCLS in which Mueller-Hinton agar and standard inoculum were used. Results indicated that all strains of S. epidermidis and S. hominis were susceptible to 1 mg desferrioxamine (the diameter of the inhibition zone were 28-37 mm). The minimum inhibitory concentrations of desferrioxamine to S. epidermidis and S. hominis isolates were determined to be 125 micrograms/ml. Further differentiation of S. hominis and S. epidermidis can be made by their ability to ferment trehalose, the former could while the latter could not. We conclude that the desferrioxamine susceptibility test of coagulase-negative staphylococci can be used in conjunction with the routine disc agar diffusion method. S. epidermidis can be identified rapidly and accurately by its susceptibility to 1 mg desferrioxamine and inability to ferment trehalose.