Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus.

This study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery of a child with NLE (21 with congenital heart disease block (CHB) and 20 with dermatologic NLE) and 19 sera from anti-Ro and/or anti-La antibody-positive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La and anti-r-Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-r-La antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (0.67 +/- 0.43 versus 0.14 +/- 0.30; P < 0.0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0.51 +/- 0.45 versus 0.83 +/- 0.37 respectively; P = 0.0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0.77 +/- 0.35) compared with non-NLE mothers (0.29 +/- 0.39; P < 0.0001). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0.82 +/- 0.37 versus 0.71 +/- 0.74; P = 0.32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (5.1 +/- 0.54 versus 2.3 +/- 0.54 respectively; P < 0.001). More importantly, when we examined the individual polypeptides, we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30% versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference in the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cutaneous basophil hypersensitivity and inhibited macrophage migration in guinea-pigs with schistosomiasis

In guinea-pigs infected with schistosomes, delayed cutaneous reactions rich in basophils (CBH) were found to characterize skin test responses to schistosome egg antigens. In addition, strong contact hypersensitivity-like skin eruptions with large basophil infiltrates resulted from skin penetration challenge by live cercariae (larvae) in these animals. Oedema and diminished basophil granule staining were noted around schistosomula which had penetrated the skin of sensitized animals. CBH responses to egg antigens and to live cercarial challenges were also noted after immunization with a single injection of dead cercariae.

Using peritoneal exudates from guinea-pigs immunized with dead cercariae or infected with schistosomes, direct macrophage migration inhibition with schistosome antigens was found only in animals with infections. Thus, CBH correlated with intradermal exposure to schistosome cercarial antigens, while MMI correlated with live infections. It is suggested that cutaneous basophil responses may play a role in protection from re-infection with schistosomes, and that dead cercarial vaccines might stimulate this beneficial response, without immunizing for potentially harmful granulomatous hypersensitivity.

     

Inhaled latex allergen (Hev b 1)

BACKGROUND: IgE-mediated responses to natural rubber latex allergens have become a major health problem among recognized risk groups. OBJECTIVE: The purpose of this investigation was to measure the amounts of Hevea brasiliensis latex allergen (Hev b 1) inhaled and deposited on surfaces when latex or vinyl gloves were worn and compare the results with the conventional measures (breathing zone samplers) of occupational exposure. METHODS: Hev b 1 exposure was measured by nasal sampling and breathing zone sampling. Latex allergen exposure was generated by having each subject don a pair of powdered latex examination gloves and continuing his or her normal daily activity for 30 minutes. By means of adhesive tape, surface dust samples were collected from the surfaces of gloves, the subject's hands, and work areas. Sampling was performed with subjects wearing no gloves, subjects wearing powdered vinyl gloves, subjects wearing powdered latex gloves, and nearby colleagues wearing latex gloves. All samples were assayed through use of the HALOgen assay (Inhalix, Sydney, Australia) with a Hev b 1-specific mAb. Particles transporting latex allergen were identified by a surrounding immunostain halo, and these were quantified and reported as total numbers of particles inhaled, airborne, or found on surface areas evaluated. RESULTS: Study subjects inhaled 26 times more allergen when powdered latex gloves were worn than under the "no glove" and powdered vinyl glove conditions. During the same period, Hev b 1 particle levels measured in the ambient air through use of the breathing zone sampler increased by 24-fold. The median numbers of particles carrying Hev b 1 allergen per square centimeter on the surface of the hands after the wearing of latex and vinyl gloves were 1964 and 5, respectively. Latex allergen was physically associated both with cornstarch granules and with larger dust particles having a darker, more irregular appearance. CONCLUSION: In a laboratory where gloves are worn for protection, the use of latex gloves resulted in a 26-fold increase in inhaled latex allergen over background levels measured while vinyl gloves were worn as controls. Low levels of latex exposure also occurred when vinyl gloves or no gloves were worn; the reasons for this are under investigation.     

Kinetics of viremia and acute liver injury in relation to outcome of neonatal woodchuck hepatitis virus infection

The kinetics of serum viral responses and acute liver injury were studied during neonatal woodchuck hepatitis virus (WHV) infection in relation to the chronic or resolved outcome. The mean concentrations of serum WHV DNA and surface antigen were significantly higher by week 10 post infection in chronic infections compared to resolving infections, and diverged even further by the time of peak viral load development in serum (week 12). After week 12, these viral markers were detected less frequently with time and at lower concentrations in the resolved outcome. In both outcomes, mean serum activities of hepatic enzymes became increased significantly above baseline by weeks 10-12, peaked at week 14, and normalized by weeks 20-22, thus indicating transient acute liver injury. The increasing liver injury responses were comparable between outcomes at week 12, when serum viral load was markedly higher in the developing chronic infections. This suggested a deficiency in early non-cytolytic control of infection in the chronic outcome. At week 14, liver injury was significantly greater in the resolved outcome and associated with higher mean Fas ligand (FasL) and perforin messenger RNAs (mRNAs) in liver compared to the chronic outcome. This indicated greater immune-mediated killing of infected hepatocytes during resolution. Thus, chronicity as an outcome of neonatal WHV infection develops relatively early during the acute phase of infection due to reduced immune-mediated clearance of infected hepatocytes by both cytolytic and non-cytolytic processes.     

Interobserver variation in the reporting of cervical colposcopic biopsy specimens: comparison of grading systems.

AIMS: To assess interobserver variation in reporting cervical colposcopic biopsy specimens and to determine whether a modified Bethesda grading system results in better interobserver agreement than the traditional cervical intraepithelial neoplasia (CIN) grading system. METHODS: One hundred and twenty five consecutive cervical colposcopic biopsy specimens were assessed independently by six histopathologists. Specimens were classified using the traditional CIN grading system as normal, koilocytosis, CIN I, CIN II, or CIN III. The specimens were also classified using a modified Bethesda grading system as either normal, low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). Participants were also asked to categorise biopsy specimens by the CIN system with the addition of the recently proposed category "basal abnormalities of uncertain significance (BAUS)". The degree of agreement between participants was assessed by kappa statistics. RESULTS: Using the CIN system, interobserver agreement was generally poor: unweighted and weighted kappa values between individual pairs of observers ranging from 0.05 to 0.34 (average 0.20) and from 0.20 to 0.54 (average 0.36), respectively. With the modified Bethesda system, interobserver agreement was better but still poor: unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36), respectively. There was little or no agreement between observers in the diagnosis of BAUS. CONCLUSIONS: Interobserver agreement in the reporting of cervical colposcopic biopsy specimens using the CIN grading system is poor. Agreement, while still poor, is better when a modified Bethesda grading system is used. There is little or no consensus in the diagnosis of BAUS.     

A UV/visible spectroscopic study of water-soluble conjugated polyenes prepared via the ring-opening metathesis polymerization reaction

A series of water-soluble conjugated polyenes, based on the poly(furanylvinylene) structure, have been prepared from readily available starting materials using ring-opening metathesis polymerization followed by dehydrogenation of the resulting polymer. ¹³C NMR analysis of the precursor polymers shows that the stereochemistry of the main-chain double bonds varies from 93% trans to 10% trans and is retained in the water-soluble derivatives, allowing different degrees of extended conjugation. This is reflected in the UV/vis spectra of the materials. The polymers may be cast into films from aqueous solution, and the UV/vis spectra exhibit vibrational fine structure indicative of conformational rigidity; significantly this fine structure is retained on redissolving the high-trans but not the high-cis films. The absorption maximum of the visible spectrum shows a stronger pH dependence in the high-cis polymers than in the high-trans, and this is interpreted in terms of the different modes of hydrogen bonding which cis and trans units can adopt.     

Congenital central hypoventilation syndrome and Hirschsprung''s disease in half sibs.

We report two infants with congenital central hypoventilation syndrome and Hirschsprung's disease who have the same father but different mothers. The genetic implications of these cases are discussed.