Novel IgE peptide-based vaccine prevents the increase of IgE and down-regulates elevated IgE in rodents

BACKGROUND: Immunotherapy with anti-IgE antibodies for treatment of allergy is promising but a short half-life and extremely high cost limit its application. OBJECTIVE: We sought to develop IgE vaccines that induce longer-lasting auto-antibodies to neutralize self-IgE as an alternative therapy. METHODS: The vaccine was made by conjugating three synthetic peptides corresponding to human IgE receptor-binding sites to a carrier, hepatitis B surface antigen. To test the immunogenicity of the vaccine, rats were immunized with the vaccine or hepatitis B surface antigen as control. Serum IgG titres to human IgE and the IgE of other species were measured. The inhibition by rat antisera of the binding of human IgE to its receptor was assessed by ELISA, flow cytometry analysis, and passive cutaneous anaphylaxis (PCA), and its ability to recognize receptor-bound IgE was examined. The in vivo effect of the vaccine was evaluated in trichosanthin-sensitized mice and rats. In the preventative study, vaccination started before sensitization commenced, while in the treatment study, vaccination started after sensitization. Sensitized mice and rats receiving injections of the carrier served as controls. Trichosanthin-specific IgE was measured using PCA. RESULTS: Sera from vaccine-immunized rats contained high titre antibodies that reacted with soluble and plate-bound but not with receptor-bound human IgE; they also reacted with mouse, rat, and dog IgE. Furthermore, the sera inhibited the binding of human IgE to its receptor in a dose-dependent manner. In preventative and treatment studies, serum trichosanthin-specific IgE levels were significantly reduced in vaccinated groups compared with controls. CONCLUSION: Antibodies against self-IgE can be induced by IgE peptide-based vaccines, which are effective in preventing the increase of IgE and in down-regulating IgE in sensitized animals.     

Brucellosis of the spine

Eight cases of spinal brucellosis are included in this study. Diagnosis was established by positive serology. Back pain was the most common complaint. Functional disturbance in walking was observed in three cases; in two others this was because of impairment of cord function. Clinical hepatosplenomegaly was found in one case. Subclinical organomegaly was diagnosed in two other patients. Psoas abscess was identified by computed tomographic scan in two separate cases. Response to drug therapy and surgical decompression, when indicated, resulted in complete recovery in all patients.     

Differential effects of galactose-induced cataractogenesis on the soluble crystallins of rat lens

Soluble lens crystallins from 6-10-week-old, galactose-fed, male Sprague-Dawley rats were analyzed by two-dimensional polyacrylamide gel electrophoresis at each of the five Sippel stages of cataractogenesis. Electrophoretograms were compared with similarly analyzed crystallins from comparably aged, chow-fed controls. Polypeptides were assigned to crystallin families and subfamilies on the basis of chromatographic fractionations with Sephadex G-200, superfine. Staining intensities of polypeptides from control lenses remained essentially unchanged throughout the experimental period, while those of the polypeptides from cataractous lenses showed non-uniform changes. Staining of the genomic gamma-crystallins increases up to at least stage 3; by stage 4, staining of gamma-chains, with perhaps those of gamma 5 and gamma 6 excepted, diminishes and in the total cataract, staining of all chains is further reduced. With possibly the addition of one chain, the total number of postsynthetically modified gamma-crystallins in cataractous lenses does not exceed that in the comparably aged normal lens. The genomic alpha- and beta-crystallin polypeptides are sustained close to normal levels up to stages 3 or 2, respectively, after which their gradually falling levels are accompanied by the generation of new species or elevated levels of existing post-translational species. An exception to this behavior is the rapid and total loss of beta B1a, a genomic subunit implicated in the aggregation of beta H-crystallins. Charge heterogeneity and variable pI displayed by beta B1a and other highly cationic beta- and gamma-crystallin polypeptides can be induced during isoelectric focusing and may be due to thiol group oxidation.     

The different effects of Helicobacter pylori strains on basal and histamine-stimulated acid and pepsin production: An in vitro study

Inflammation Research -     

Effect of (+/-)-, (+)- and (-)-gossypol on the lactate dehydrogenase-X activity of rat testis

The effect of (+/-)-, (+)- and (-)-gossypol on testicular lactate dehydrogenase-X (LDH-X) was studied in vitro and in vivo. It was found that racemic gossypol and the two optical enantiomers had similar inhibitory effects on rat testicular LDH-X in vitro. However, neither racemic gossypol nor the enantiomers exhibited an inhibitory effect on testicular LDH-X in vivo. It is concluded that inhibition of testicular LDH-X is not likely to be the mechanism of the antifertility action of gossypol. The inhibition of testicular LDH-X in vitro by all three preparations of gossypol is probably non-specific.     

Optimizing Suicide Gene Therapy for Head and Neck Cancer

An effective “suicide gene” therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene(HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 × 10⁸ to 2 × 10⁹ plaque forming units(pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials.     

人精液中ABH血型物质分泌强度的研究

本文采用中和试验、沉降反应和解离试验对１３５例已知血型人精液中ＡＢＨ血型物质的分泌强度进行了检验，并将其分为强、中、弱三型。这对区别个人血型物质含量及性犯罪的法医学鉴定均有重要意义。并证明了ＡＢ型人精液中Ａ、Ｂ血型物质含量不均等现象，并且绝大多数人Ｂ型物质高于Ａ型物质。