Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries.

Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics - population testing number and testing coverage - to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = -0.79, P = 5.975 × 10-9vs. rs = -0.3, P = 0.05) and case fatality rate (rs = -0.67, P = 9.067 × 10-6vs. rs = -0.21, P = 0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.

Effect of chlorhexidine bathing on colonization or infection with Acinetobacter baumannii: a systematic review and meta-analysis.

Healthcare-associated infections (HAIs) caused by multi-drug-resistant Gram-negative bacteria (MDRGNB) have increased prevalence in intensive care units (ICUs). A common strategy to prevent HAIs is bathing patients with chlorhexidine gluconate (CHG). However, the effectiveness of CHG bathing against multidrug-resistant Acinetobacter baumannii (MDRAB) is still controversial. The aim of this study was to perform a systematic review and meta-analysis of the effectiveness of CHG bathing on Acinetobacter baumannii colonization and infection in the ICU setting. A systematic literature search of PubMed, EMBASE, Web of Science and CINAHL was performed from inception through to June 2018. Randomized controlled trials (RCTs), pre-post studies, or interrupted time series (ITS) studies were included. The numbers of patients with/without colonization or infection of A. baumannii in the experimental or control groups were extracted from each study. Quality assessment was performed by the related instruments of National Institute of Health. Pooled risk ratios (RRs) were calculated using the random-effects model. One RCT and 12 pre-post or ITS studies comprising 18,217 patients were included, of which 8069 were in the CHG bathing arm and 9051 in the control arm. CHG bathing was associated with a reduced colonization of A. baumannii (RR, 0.66; 95% confidence interval: 0.57-0.77; P<0.001). Chlorhexidine at 4% showed a better effect than 2% chlorhexidine (meta-regression P=0.044). CHG bathing was associated with a non-significant reduction of infection (pooled RR 0.41, 95% CI: 0.13-1.25). This study suggests that CHG bathing significantly reduces colonization of A. baumannii in the ICU setting. However, more trials are needed to confirm whether CHG bathing can reduce infections with A. baumannii.

Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis.

OBJECTIVES: To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)-BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays-on the detection of viral respiratory infections. METHODS: A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay. RESULTS: Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848-0.949), 0.949 (95% confidence interval, 0.882-0.979) and 0.954 (95% confidence interval, 0.871-0.985), respectively. The three mPCRs were comparable in terms of detection of FluA. CONCLUSIONS: Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.

Preadmission statin use improves the outcome of less severe sepsis patients - a population-based propensity score matched cohort study.

BACKGROUND: Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied. METHODS: We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications. RESULTS: We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78-0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78-0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission. CONCLUSIONS: In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

Mutagen sensitivity as measured by induced chromatid breakage as a marker of cancer risk.

Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in the chromosomes of peripheral blood lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related maladies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by clastogenic agents, such as the γ-radiation mimetic DNA cross-linking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-nitroquinoline and the tobacco smoke constituent benzo[a]pyrene, in short-term cultured peripheral blood lymphocytes.

High-voltage thin-film GaN LEDs fabricated on ceramic substrates: the alleviated droop effect at 670 W/cm(2).

High-voltage thin-film GaN LEDs with the emission wavelength of 455 nm were fabricated on ceramic substrates (230 W/m · K). The high-voltage operation was achieved by three cascaded sub-LEDs with dielectric passivation and metal bridges conformally deposited on the side walls. Under the driving power of 670 W/cm(2), the high-voltage LEDs exhibit much alleviated efficiency droop and the operative temperature below 80 °C. The excellent performances were attributed to the improved current spreading within each sub-LED and the superior heat sinking of the ceramic substrate.

Profiles of circulating endothelial cells and serum cytokines during adjuvant chemoradiation in rectal cancer patients.

INTRODUCTION: This research aimed to demonstrate the correlation of circulating endothelial cells (CECs) count and serum cytokine levels with side effects and prognosis in rectal cancer patients receiving adjuvant chemoradiation. METHODS: Eleven patients received proctectomy, chemoradiotherapy and follow-up for 4 years. Fifty-five blood samples were taken before radiation and during the course. The quantities of CECs were estimated by flow cytometry, and serological factors were measured by ELISA. RESULTS: The CEC level in patients without tumor recurrence was significantly lower than in patients with tumor recurrence (p < 0.01). The IL-6 and TGF-ß1 levels exhibited a similar profile (p < 0.01). For morbidity, the mean CEC level in patients with grade 3 diarrhea was significantly greater than patients with grades 1 (p < 0.001) and 2 diarrhea (p < 0.005). CONCLUSIONS: Levels of CECs, serum IL-6, TGF-ß1 and TNF-α during post-operative chemoradiation in rectal cancer patients might be candidate biomarkers for prognosis and morbidity (NCT00325871).

The association of psychosocial factors and smoking with periodontal health in a community population.

BACKGROUND AND OBJECTIVE: The association between psychosocial factors and periodontal disease has been widely reported and might be modified by smoking status. This study investigated the association of periodontal status with psychosocial factors and smoking in a community population. MATERIAL AND METHODS: A structured questionnaire was administered to a total of 1,764 civilian noninstitutional (general population excluding from nursing homes, sanitariums and hospitals) Taiwanese individuals to assess the presence and severity of psychosocial factors [using the 12-item Chinese health questionnaire (CHQ-12)], smoking habits and other related factors. Periodontal status was established using the community periodontal index and by measuring clinical loss of attachment. RESULTS: Psychological factors and smoking were significantly associated with loss of attachment (odds ratio = 1.69, 95% confidence interval = 1.01-2.77, comparing the CHQ-12 score of >or= 6 with the CHQ-12 score of 0-2 and p = 0.032 for linear trend; odds ratio = 2.21, 95% confidence interval = 1.45-3.37, comparing smokers with nonsmokers) but not with community periodontal index. The association was found to be stronger among smokers than among nonsmokers. Smokers with a CHQ-12 score of >or= 6 had a higher odds ratio of loss of attachment (odds ratio = 2.49, 95% confidence interval = 0.91-6.49) than nonsmokers (odds ratio = 1.43, 95% confidence interval = 0.76-2.58). For periodontal health measured using the community periodontal index, married and divorced/widowed subjects tended to have poorer periodontal health (odds ratio = 3.38, 95% confidence interval = 1.26-10.81 and odds ratio = 3.83, 95% confidence interval = 1.21-13.83, respectively) than single subjects among nonsmokers but not among smokers. CONCLUSION: Poor mental health had a stronger association with periodontal disease among smokers than among nonsmokers, especially in accumulative attachment loss. Our findings suggest that mental health and smoking might have a synergistic effect on the risk of developing periodontal disease.

4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of nonmelanoma skin cancer: a case-control analysis.

The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case-control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 microM for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean+/-SD, 0.46+/-0.43 for SCC and 0.43+/-0.38 for BCC) than in the controls (0.25+/-0.25; P<0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.

Anti-PCNA autoantibodies preferentially recognize C-terminal of PCNA in patients with chronic hepatitis B virus infection.

We previously reported anti-PCNA autoantibodies in sera from patients with chronic HBV and HCV infection. To analyse the antigenic regions on proliferating cell nuclear antigen (PCNA) that confer autoantibody binding in patients with chronic hepatitis B (HBV) and C (HCV) infection, eight constructs including one wild type PCNA, one mutant type Y114A_PCNA and six C- or N-terminal PCNA truncations were generated. Sera from 185 patients with systemic lupus erythematosus (SLE), 178 with chronic HBV and 163 with chronic HCV infection, and 68 healthy individuals were examined for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA). By ELISA, anti-PCNA positive sera from patients with SLE, chronic HBV and HCV infection preferentially recognized the wild type PCNA more than the mutant type Y114A_PCNA (P < 0.05). The inhibition of binding by purified full-length rPCNA proteins with anti-PCNA positive sera was shown to exceed 70%. The inhibition of binding by purified truncated rPCNA proteins with sera from patients with chronic HBV and HCV infection and SLE was shown to confer dominant binding in T(L2) and T(L3). Moreover, the higher frequency of inhibition by using T(L3) was found in patients with chronic HBV infection. These data indicate that anti-PCNA autoantibodies preferentially recognize C-terminal of PCNA in patients with chronic HBV infection and may also provide advanced understanding between viral infection and autoimmunity for further study.

Increased expression and secretion of interleukin-6 in human parvovirus B19 non-structural protein (NS1) transfected COS-7 epithelial cells.

Human parvovirus B19 (B19) has been associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We have demonstrated previously that B19 non-structural protein (NS1) induced apoptosis through the mitochondria cell death pathway in COS-7 epithelial cells and that B19 NS1 may play a role in the pathogenesis of autoimmune diseases. In order to examine the expression profiles of cytokines and chemokines in B19 NS1 transfected COS-7 cells, we constructed the NS1 gene in the pEGFP-C1 vector named enhanced green fluorescence protein gene (EGFP)-NS1. COS-7 cells were transfected with EGFP or EGFP-NS1 plasmid. The expression profiles of cytokines and chemokines, including interleukin (IL)-1beta, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, granulocyte-macrophage colony-stimulating factor (GM-CSF), growth-related oncogene alpha (GROalpha), interferon gamma-inducible protein (IP)-10, stromal cell derived factor (SDF)-1, macrophage inflammatory protein (MIP)-1beta, monocyte chemoattractant protein (MCP)-1, regulated upon activation normal T cell expressed and secreted (RANTES), Fractalkine, CX3CR1, CCR2, CCR5 and CCR11 were examined in COS-7 cells, EGFP and EGFP-NS1 transfected cells using enzyme-linked immunosorbent assay (ELISA) or reverse transcription-polymerase chain reaction (RT-PCR). Increased expression and levels of IL-6 were found in EGFP-NS1 transfected cells using RT-PCR and ELISA. There were no significant increases in the expression of IL-1beta, IL-8, IP-10, SDF-1, RANTES, Fractalkine, CX3CR-1, CCR2, CCR5, CCR11, TNF-alpha, GM-CSF and TGF-beta using RT-PCR. There were no significantly increased levels of IL-5, IL-10, TNF-alpha, TGF-beta, GROalpha, MIP-1beta and MCP-1 found by ELISA in this study. Our results show that increased expression and secretion of IL-6 in B19 NS1 transfected epithelial cells may play a role in the pathogenesis of autoimmune diseases.

Mutagen-induced chromatid breakage as a marker of cancer risk.

Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in peripheral lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related malignancies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by chromosome breaking agents, such as the gamma-radiation radiomimetic DNA crosslinking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-NQO and the tobacco smoke constituent, benzo[a]pyrene, in short-term cultured peripheral blood lymphocytes.

Severe hemophilia A due to a 1.3 kb factor VIII gene deletion including exon 24: homologous recombination between 41 bp within an Alu repeat sequence in introns 23 and 24.

Partial or complete factor (F)VIII gene deletions are found in about 5% of families with severe hemophilia A. Relatively few deletions have been well characterized and, of these, recombination occurred between either common repeat elements or non-homologous sequences. In evaluating a family with severe hemophilia A, an exon 24 deletion was suspected when no fragment was obtained on attempted PCR amplifications. A combination of the 5' primer of exon 23 and the 3' primer of exon 25 fragments was used with prolonged extension times to amplify a normal 2.9 kb fragment that included exons 23 through 25; the patient's amplified product was 1.6 kb indicating a 1.3 kb deletion. A mixture of normal and patient DNA showed both sized fragments as did that from an obligate carrier. Carrier detection was applied to two women at risk; one was and one was not a carrier. Sequencing the proband's 1.6 kb fragment revealed that a 1328 bp deletion occurred between homologous sequences of 287 and 285 bp in introns 23 and 24, respectively; these share 85% identity. Blast nucleotide search revealed that these represent Alu elements. Comparison with an alignment of each of the two homologous sequences further localized recombination to a 41-bp segment. However, a simple recombination event would not account for the proband's sequence. The most likely explanation is that the homologous recombination was accompanied by incomplete mismatch repair.

Anti-nuclear antibody, anti-DNA, and aCL in Graves' disease patients treated with propyluracil or methimazole.

One hundred and forty patients with Graves' disease [32 new patients, 54 treated with propylthiouracil (PTU) for a mean of 27.2 months and 54 treated with methimazole (MMI) for a mean of 48.6 months] were tested for anti-thyroid microsomal antibody (AMA), anti-thyroglobulin antibody (ATA), thyroid binding inhibitory immunoglobulin (TBII), and the non organ specific autoantibodies [i.e., anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA Ab), anti-cardiolipin antibody (aCL Ab) and anti-beta2-glycoprotein I antibody (IgG beta2GPI)]. Treatment with MMI or PTU produced a significant difference in IgG aCL Ab production but not in ANA, dsDNA Ab, IgM aCL or IgG beta2GPI. For those treated with MMI but not those treated with PTU, ANA and anti-dsDNA Ab were positively correlated. IgG and IgM aCL Ab were positively correlated overall and for those on MMI but not PTU treatment. No significant difference was found for any of the four non organ specific antibodies in AMA positive or negative patients but there was a significant difference in IgG aCL positivity rates for ATA positive and negative patients. On the other hand, ANA negative patients were significantly more likely to have higher TBII values. These results suggest that the appearance of the non organ specific autoantibodies is probably largely a coincidental effect of polyclonal activation - except, perhaps, for IgG aCL, which may be related to treatment.

Germline Telomere Length Dynamics and Mutagen Sensitivity Studies in a Family with Acute Reactions to Sun Exposure: Involvement of Three Generations.

Most cancers are the result of an interaction between germline genetic susceptibility and exposure to environmental carcinogens. We studied chromosomal aberrations, telomeric associations, telomere signal intensity by fluorescence in situ hybridization, p53 germline mutation, bleomycin (Bleo) and 4-nitroquinoline-1-oxide (4NQO) sensitivity, and chromosome-specific telomere signals in T and B lymphocytes in a Caucasian family involving three generations and 13 family members. This family was chosen because eight of its members are extremely sensitive to sunlight and burn easily even upon short exposure. The family members have shown: (a) hypersensitivity either to Bleo or 4NQO mutagens, with values much higher than 1.00 breaks/cell (b/c) for Bleo and 0.40 b/c for 4NQO; (b) an increased rate of telomeric associations; (c) variable amounts of telomeric DNA not common for the person's age; (d) the presence of intron 7 polymorphism in the proband and no significant effect on N-methyl-N'-nitosoguanidine (MNNG)-induced p53 expression in two key family members; and (e) an incidence of epithelial malignancies in two family members. Seven additional members showed polymorphism of telomeric signals in the short arm of two homologous chromosome 17s, where the p53 gene is localized. A 78-year-old grandmother, who had developed colon cancer, was predicted to have metastatic cancer based on the telomeric DNA amount in her lymphocytes (2.90%); she subsequently developed metastatic lesions within a year and died. Based on these observations, we conclude that telomere erosion is the initial cause of genomic instability/susceptibility which, in turn, may be causal for the reproductive complications, premature aging phenotypes and, in some cases, predisposition to cancer development.

Genetic instability of specific chromosomes associated with a family history of cancer.

This study evaluated the association between family history of cancer and bleomycin-induced mutagen breaks at specific chromosomes. The authors' hypothesis was that individuals exhibiting mutagen-induced specific chromatid breaks might have genetic instability and thus be more likely to report a family history of cancer. The study included 78 healthy individuals. All subjects completed a personal interview to collect epidemiologic information, including a detailed family history of cancer, and donated a 10-mL blood sample. Bleomycin-induced mutagen sensitivity on specific chromosomes was quantified by counting the bleomycin-induced specific chromosomal breaks with Q-banding techniques. We found that chromosome 4 breaks were significantly associated with a positive family history of cancer in first-degree relatives with an odds ratio of 3.18 and 95% confidence interval of 1.05-9.61. However, none of the other chromosomes showed significantly increased risk with family cancer history. In addition, the mutagen-induced chromosome 4 breaks were not associated with age, sex, ethnicity, or smoking status. These findings suggested that chromosome 4 mutagen sensitivity might be a predictor of familial susceptibility to cancer.

Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) infection has been found to be strikingly associated with autoimmune phenomena. The aim of the present study was to investigate the presence of various autoantibodies in patients with HCV infection. Anti-neutrophil cytoplamic antibody (ANCA), anti-dihydrolipoamide dehydrogenase (anti-E3), rheumatoid factor (RF), anti-dihydrolipoamide acetyltransferase (anti-E2), anti-SS-A/Ro (60 kD), anti-SS-A/Ro (52 kD), anti-SS-B/La, anti-topoisomerase II (anti-topo II), anti-cardiolipin (aCL), anti-dsDNA, anti-ssDNA, anti-nuclear antibodies (ANA), anti-proteinase 3 (anti-Pr3) and anti-myeloperoxidase (anti-MPO) were determined in sera from 516 patients with HCV infection, 11 with primary biliary cirrhosis (PBC) and 44 healthy controls. Assays employed were indirect immunofluoresence, the particle latex agglutination test, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. ANCA, anti-E3 antibody and RF were positive in 278/516 (55.6%), 276/516 (53.3%) and 288/516 (56%) patients with HCV infection, respectively. Positivity for ANA was present in 15.8%, anti-ssDNA in 15.6%, anti-dsDNA in 8.5%, aCL in 5%, anti-SS-B/La in 4.1%, anti-SS-A/Ro (60 kD) in 3.9%, anti-E2 in 3.3% and anti-SSA/Ro (52 kD) in 1.2%, anti-MPO in 4.8%, anti-Topo II and anti-actinin in 0%. All sera with ANCA showed c-ANCA patterns and contained anti-PR3 specificity. HCV patients with ANCA showed a higher prevalence of skin involvement, anaemia, abnormal liver function and alpha-Fetoprotein (alpha-FP). HCV patients with anti-E3 antibodies showed a higher prevalence of liver cirrhosis, arthritis, abnormal liver function and elevated alpha-FP levels. The prevalence of autoantibodies was not affected by treatment with interferon-alpha (IFN-alpha). In conclusion, autoantibodies are commonly found in patients with HCV infection. There is a high prevalence of anti-E3, ANCA and RF in these patients. Proteinase 3 and E3 are the major target antigens in HCV infection. HCV may be regarded as a possible causative factor in ANCA-related vasculitis.

Heterochromatin and interstitial telomeric DNA homology.

The purpose of this investigation was twofold. The first objective was to demonstrate that, in most of ten mammalian species commonly used in biomedical research, not all constitutive heterochromatin (C-bands) represents telomeric DNA. For example, the C-bands in human chromosomes, the long arm of the X and the entire Y chromosome of Chinese hamster, and most of the short arms of Peromyscus and Syrian hamster chromosomes are not telomeric DNA. In addition to the usual terminal telomeric DNA in the chromosomes of these mammalian species, the pericentromeric regions of seven or eight Syrian hamster chromosomes and all Chinese hamster chromosomes except pair one have pericentromeric regions that hybridize with telomeric DNA, some in C-bands and some not. The second objective was to describe a simple fluorescence in situ hybridization (FISH) reverse-printing procedure to produce black-and-white microphotographs of metaphase and interphase cells showing locations of telomeric DNA with no loss of resolution. Thus, at least three different types of heterochromatin (telomeric heterochromatin, nontelomeric heterochromatin and a combination of both) are present in these mammalian species, and this simple black-and-white reverse printing of telomeric FISH preparations can depict them economically without sacrificing clarity.

Epitope mapping of factor VIII inhibitor antibodies of Chinese origin.

Epitopes recognized by factor VIII (FVIII) inhibitors of Chinese origin were analysed by immunoblotting with full-length recombinant FVIII (rFVIII), thrombin-activated FVIII (FVIIIa) and 16 FVIII fusion proteins synthesized by bacteria. Twenty-eight patients, 12 with haemophilia A and 16 with autoimmune diseases, were recruited. Antibodies from 22 patients showed reactivity with rFVIII, 20 with FVIIIa, and one reacted only with FVIII fusion proteins. Of these 22 cases, most were reactive with A2-a2 and A3-C1-C2 of FVIII(a). Of the nine cases that depicted binding to the fusion proteins, three were reactive with the A domains, three with only the B domain, and the other three with both the A and B (or C) domains. An epitope for a neutralizing antibody of a haemophilia A patient, designated TWN-112, was localized to residues 323-390, specified by FVIII fusion proteins. The same epitope also appeared on an FVIII-expression phage library screening. Immunoabsorption of antibodies from TWN-112 with the epitope reduced the neutralizing activity of the inhibitor by 33%. The incidence of a1 of FVIII is higher, and that of a3 is lower, than previously reported. Two novel epitopes, reported for the first time in this paper, were localized on the 8B2 (amino acid residues 1022-1204) and 8A2(V) (residues 673-740) fusion proteins. These two epitopes were able to reduce inhibitory antibody activity by 24% and 25% respectively. Changes of FVIII fragment specificity were also observed in one of six patients for whom multiple samples, collected at different times, were available. Our initial finding showed that the FVIII inhibitors in these Chinese patients shared epitopes with those of patients from very different genetic backgrounds, suggesting a common mechanism for the development of FVIII inhibitors.