Studies of Antibody to Herpes Simplex Virus Fcγ-Binding Protein gE in Patients with Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis and Normal Controls

IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins.     

Effect of Group A Streptococcal Cysteine Protease on Invasion of Epithelial Cells

Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had the ability to invade A-549 human respiratory epithelial cells. Isogenic protease mutants were constructed by using integrational plasmids to disrupt the speB gene and confirmed by Southern hybridization and Western immunoblot analyses. No extracellular protease activity was produced by the mutants. The mutants had growth rates similar to those of the wild-type strains and produced normal levels of other extracellular proteins. When invading A-549 cells, the mutants had a two- to threefold decrease in activity compared to that of the wild-type strains. The invasion activity increased when the A-549 cells were incubated with purified cysteine protease and the mutant. However, blockage of the cysteine protease with a specific cysteine protease inhibitor, E-64, decreased the invasion activity of GAS. Intracellular growth of GAS was not found in A-549 cells. The presence or absence of protease activity did not affect the adhesive ability of GAS. These results suggested that streptococcal cysteine protease can enhance the invasion ability of GAS in human respiratory epithelial cells.     

Identification of Candida albicans by specific primers of polymerase chain reaction and DNA probes

Candida albicans is a pathogenic yeast. Two sets of universal primers were used for specific identification of Candida albicans with PCR-amplified ribosomal DNA internal transcribed spacers (ITS). Among the species of Candida, the amplified ITSI and ITSII of DNA fragments were similar in size. The PCR product was purified and labeled with digoxigenin and used as DNA probe in the detection with target DNA of Candida albicans by hybridization. Two sets of specific primers (CA1 and CA2 to amplify ITSI, CA3 and CA4 to amplify ITSII) were designed by alignment of ribosomal ITS sequence of pathogenic Candida albicans with other species to detect C. albicans by PCR. The sensitivity of PCR using the specific primers to detect pure culture of C. albicans was 0.1 ng (about 10(3)-10(4) cells). If the yeast cells were mixed with two other strains, there was a 10-fold decrease in sensitivity (1 ng or 10(4)-10(5) cells) under the same PCR conditions.     

Anti-tumor immunoglobulin M increases lung metastasis in an experimental model of malignant melanoma

Cancer metastasis involves distinct steps that depend on complicated tumor–host interactions. The hematogenous dissemination of tumor cells may be facilitated by factors that promote the arrest and adherence of cancer cells in capillaries. We examined whether anti-tumor monoclonal immunoglobulin M (IgM) antibodies promoted the hematogenous dissemination of B16 melanoma cells in syngeneic mice. IgM monoclonal antibodies were generated that selectively bind to B16 melanoma cells as compared to syngeneic fibroblasts, lymphocytes or Lewis lung carcinoma cells. Incubation of B16-BL6 or B16-F0 melanoma cells with these IgM anti-tumor antibodies significantly increased the number of lung colonies as compared with control antibodies. Moreover, intraperitoneal injection of specific antibody also significantly increased lung colonization. All anti-tumor antibodies promoted the aggregation of B16 melanoma cells. A chemically generated immunoglobulin G (IgG)-like fragment of an anti-tumor IgM antibody displayed greatly reduced tumor aggregation and, in contrast to intact IgM, did not significantly increase lung colonization of B16 melanoma cells. Neither intact IgM nor the IgG-like fragment enhanced the in vitro invasiveness of B16 melanoma cells across Matrigel-coated membranes. Our results, therefore, suggest that besides their beneficial anti-tumor effects, anti-tumor IgM antibodies may also promote the hematogenous dissemination of cancer cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Abrupt temperature change triggers arthralgia in patients with juvenile rheumatoid arthritis.

BACKGROUND AND PURPOSE: Juvenile rheumatoid arthritis (JRA) is the most common form of arthritis in children and affects both quality of life and school attendance. Weather and temperature conditions are believed to affect joint pains; however, very few studies have investigated this issue. This study examined the association between joint pain in JRA patients and weather conditions. METHODS: The daily pain ratings of 52 patients previously diagnosed with JRA were recorded on visual analog scales over 4 months beginning January 1, 2004. These ratings were then compared with weather data to evaluate possible correlation between these two factors. RESULTS: Twenty nine patients kept daily records during the first 2 months. There was no positive correlation between weather parameters (such as temperature, humidity, and barometric pressure) and pain ratings. Interestingly, the pain rating significantly increased the day after the advent of a cold wave (sign test, p<0.01; Wilcoxon signed ranks test, p=0.001). The number of patients who experienced joint swelling was not related to weather conditions. Twenty one participants continued maintaining the diaries during the next 2 months. The patients reported higher pain levels in the first 2 months during the cold wave period than in the next 2 months when the cold wave period had ended (p<0.001). CONCLUSION: A dramatic weather change such as a sudden cold wave might influence the experience of joint pain.     

Epidemiologic relationship between fluoroquinolone-resistant Salmonella enterica Serovar Choleraesuis strains isolated from humans and pigs in Taiwan (1997 to 2002)

The emergence of ciprofloxacin-resistant Salmonella enterica serovar Choleraesuis in recent years has become an important public health issue in Taiwan. The resistant strains that cause human infections are considered to be from pigs. In this study, we characterized 157 swine and 42 human Salmonella serovar Choleraesuis isolates by pulsed-field gel electrophoresis (PFGE) and drug susceptibility testing to investigate the epidemiologic relationship among the isolates. By PFGE analyses, two major clusters (clusters GA and GB) were identified. Isolates in cluster GA were of both human and swine origins, while those in cluster GB were from pigs only. Among the various genotypes identified, genotype gt-1a was the most prevalent, which was found in 71% (30 of 42) and 48% (76 of 157) of human and swine isolates, respectively. The susceptibility tests for the 106 gt-1a isolates identified 44 susceptibility profiles and showed that 73% of human isolates and 34% of swine isolates were resistant to three fluoroquinolones (ciprofloxacin, enrofloxacin, and norfloxacin). Our findings indicate that a clonal group of Salmonella serovar Choleraesuis may have been circulating in human and swine populations in Taiwan for years and that the fluoroquinolone-resistant Salmonella serovar Choleraesuis strains most likely evolved from a gt-1a clone that emerged in 2000 and that then caused widespread infections in humans and pigs. Nevertheless, it is still debatable whether those Salmonella infections in humans are caused by isolates derived from pigs, on the basis of the higher fluoroquinolone and other antimicrobial resistance percentages in human isolates than in pig isolates.