Sustained eosinophil cationic protein release into tears after a single high-dose conjunctival allergen challenge

Background The appearance of eosinophils is a hallmark sign of the allergic late-phase response (LPR). Eosinophil cationic protein (ECP), a readily measurable product released from activated eosinophils, has so far not been evaluated in the ocular LPR. Objective Two sets of trials were performed in order to investigate changes of local and systemic eosinophil activity and their possible link with symptoms and hyper-reactivity in the allergic LPR in the eye. Methods In the first experiment, ECP was analysed in tears and serum and the clinical reaction was evaluated during a 72-h time–course after a single, high-dose allergen challenge out of season in one eye of 15 pollen-sensitized volunteers. In a second experiment, the hypothesis of an increased clinical response to an allergen challenge in an eye that had been provoked with allergen 48h previously was tested in nine sensitized individuals. Results In the first experiment, symptoms at 10 min and 2, 4, 6, 8 and 24 h significantly exceeded base line scores of the challenged eyes. Tear ECP was significantly elevated in challenged eyes compared to contralateral eyes at 6, 8 and 24 h. In addition, symptoms and ECP release correlated significantly at the 24-h evaluation. Serum ECP remained unchanged throughout the study period. In the second experiment, conjunctival hyperreactivity 48h after an allergen challenge was not confirmed. Conclusion ECP secretion occurs in the experimental ocular LPR and is in part associated with the magnitude of the clinical reaction, which suggests a truly pathogenic role of the activated eosinophil in pollen-induced allergic conjunctivitis.     

Older donors and kidney transplantation

Reluctance to use kidneys from older donors (>50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation.     

Fetal growth and autoimmune thyroid disease

To determine whether fetal and infant growth could influencesusceptibility to autoimmune disease in adults, the occurrenceof thyroid autoantibodies and autoimmune thyroiditis was studiedin 305 women, aged 60–71, born in Hertfordshire and forwhom details of birth weight, infant growth, and feeding wereroutinely recorded. Thyroglobulin autoantibody was detectedin 37% of the women, thyroid peroxidase autoantibody in 41%,and autoimmune thyroiditis, defined as biochemical or clinicalhypothyroidism in association with thyroid autoantibodies, in5.6%. The proportion of women with thyroglobulin and thyroidperoxidase auto antibodies fell with increasing birth weightbut was not related to weight at 1 year of age or the methodof infant feeding. The prevalence of both autoantibodies rosewith increasing adult body mass index but fell as the waistto hip ratio increased. These results demonstrate the importance of early environmentin determining the susceptibility to autoimmune thyroid disease.The contrasting effects of adult body mass index and waist tohip ratio on antibody prevalence could be explained by theirassociations with different hormonal environments.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

胸大肌肌皮瓣在口腔颌面部缺损修复中的应用

报道２１９例口腔颌面部肿瘤，其中良性肿瘤１８例，恶性肿瘤２０１例，在肿瘤切除后，均采用胸大肌肌皮瓣修复缺损。采用单皮岛肌皮瓣２０１例，双皮岛肌皮瓣１６例，肌皮骨瓣２例。成功２０１例，失败１８例。讨论了胸大肌皮瓣的优点及适用范围。介绍了手术设计、操作方法。分析了成功与失败的影响因素，认为正确，精细的手术技巧是成功的关键因素。     

Comparative study of five different DNA fingerprint techniques for molecular typing of Streptococcus pneumoniae strains.

The aim of this study was to identify the strengths and weaknesses of five DNA fingerprint methods for epidemiological typing of Streptococcus pneumoniae. We investigated the usefulness of (i) ribotyping, (ii) BOX fingerprinting with the BOX repetitive sequence of S. pneumoniae as a DNA probe, (iii) PCR fingerprinting with a primer homologous to the enterobacterial repetitive intergenic consensus sequence, (iv) pulsed-field gel electrophoresis of large DNA fragments, and (v) restriction fragment end labeling to detect restriction fragment length polymorphism of small DNA fragments. Twenty-eight S. pneumoniae strains isolated from the blood and/or cerebrospinal fluid of 21 patients were analyzed. Genetic clustering among the 28 strains was independent of the DNA fingerprint technique used. However, the discriminatory power and the similarity values differed significantly among the individual techniques. BOX fingerprinting, pulsed-field gel electrophoresis, and restriction fragment end labeling provided the highest degree of discriminatory power. Furthermore, the ease with which computerized fingerprint analysis could be conducted also varied significantly among the techniques. Ribotyping, BOX fingerprinting, and restriction fragment end labeling were very suitable techniques for accurate computerized data analysis. Because of their high discriminatory potential and ease of accurate analysis, we conclude that BOX fingerprinting and restriction fragment end labeling are the most suitable techniques to type pneumococcal strains.     

Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation.

The present study explored the role of murine monocyte chemotactic protein (MCP) in the T cell-mediated hypersensitive granulomatous response to Schistosoma mansoni eggs. The study examined the time course of local production, contribution to cellular infiltration, and the role of T cells in endogenous regulation. Synchronized pulmonary granulomas were induced under conditions of primary and secondary states of immunity. Primer-directed polymerase chain reaction analysis showed increased MCP mRNA expression in granulomatous lungs, mainly in the secondary response. Levels of MCP were measured by enzyme-linked immunosorbent assay in cultures of intact granulomas. Spontaneous MCP production was modest in primary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accelerated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistochemical staining revealed the strongest MCP expression within microvascular adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% reduction in the secondary granuloma area but did not significantly affect the primary response. With adoptive cell transfer and T cell subset depletion, it was shown that Thy-1+ and CD5+ cells augmented, whereas CD8+ cells appeared to impair, MCP production. This provides direct evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.