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.     

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. II. Modification of early changes by platelet inhibition with aspirin and dipyridamole

The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 +/- 52 micrograms/100 mg at 90 days, 205% of the level in ungrafted vein (p less than 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2 = 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2 = 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.     

Development and testing of a decision tree for blunt trauma

The aim of the present study was to examine the essential problems in a retrospective study of 381 organ injuries in 260 patients, to identify problems, to define criteria, to describe decision rules, and to organize these rules into branch-chain decision trees or clinical algorithms. The basic hypothesis of this study is that criteria organized into a prioritized decision tree can provide objective standards to evaluate the quality of trauma care and to compare alternative approaches. The algorithm was designed to provide prompt therapy for the most life-threatening problems: respiratory and cardiac arrest, shock, head injury, tamponade, lacerations of the great vessels, cardiac contusion, ruptured parenchymal organs, lacerated viscera, and injury to other intraperitoneal organs. Resuscitation from shock, correction of circulatory problems, and monitoring of physiologic variables were prioritized to evaluate the presence of circulatory deficits and the adequacy of specific therapy to correct them. Concomitantly, diagnosis of the underlying problems was approached using peritoneal lavage, abdominal and chest x-rays, iv urograms, cystograms, endoscopy, upper and lower GI barium or hypaque studies, ultrasound, scintograms, and CT scans. In emergency conditions these are limited to a large extent by time factors. The diagnostic accuracy, priorities, and limitations of each of these were evaluated in emergency conditions. The algorithm was used to track management decisions in a prospective series; the mortality of 51 patients with satisfactory compliance was 4% and 44% in nine patients with major deviations from the algorithm.     

廊坊市农村儿童1987～1993年头胸围及交叉月龄变化的分析

本文通过对我市农村1987、1990、19933个年份中10～24月龄男女儿童头围和胸围及头胸交叉所在月龄变化的分析。表明我市农村儿童随着家庭生活水平的不断提高,其生长发育正处在长期加速阶段。同时可以看到:由于基础较差,在科学育儿方面还有较大差距,尽快克服普遍存在的落后喂养习惯和断奶食品的缺乏已成为进一步提高我市农村儿童生长发育水平的关键.应予充分重视,加以解决。     

Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.     

Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae

The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells.     

Pituitary lactotrophs endocrine, paracrine, juxtacrine, and autocrine interactions.

The synthesis and release of PRL by the lactotrophs is subjected to multiple regulators that are classified into four categories: endocrine, paracrine, juxtacrine, and autocrine. Endocrine agents originate from the hypothalamus, gonads, and the posterior pituitary. Paracrine factors are produced by cells of the intermediate and anterior lobes. Juxtacrine transmitters arise from extracellular matrix and cells adjacent to the lactotrophs. Autocrine agents are synthesized by the lactotrophs themselves. Consequently, the overall secretory activity of the lactotrophs reflects a balance between local and distant releasing and inhibiting factors.