The presence of carboxypeptidase-M in tumour cells signifies epidermal growth factor receptor expression in lung adenocarcinomas

Purpose Carboxypeptidase-M (CPM) is a membrane-bound peptidase that metabolizes peptides, and is present in pneumocytes. CPM hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg⁵³-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. Therefore, this study focused on the possible presence of CPM in human lung adenocarcinomas (ADC) and evaluated the relationship between CPM and EGFR by assessing the impact of expressions on patient clinical outcome. Methods This is a retrospective study of 110 patients who underwent resection of the primary tumour (92) or metastatic tissues (18) for treatment or diagnosis. Immunohistochemistry (IHC) for CPM and EGFR was made in serial sections using standard methods. Results This study demonstrates for the first time that 23.6% of ADCs express carboxypeptidase-M (26/110), mainly in membrane-bound forms. The amounts and the extent of CPM within tumours vary from low levels to obviously overexpressed forms. The immunohistochemical positivity (+) for CPM in ADCs negatively correlated with disease survival. In addition, 80% of CPM⁺ adenocarcinomas (21/26) showed a coexpression with EGFR suggesting a high prevalence for coexistence. The follow up data indicated a significantly shorter 5-year survival time for patients with CPM⁺–EGFR⁺ (double-positive) tumours compared to those harbouring neoplasias negative for both proteins (9.5 vs. 60.4% survivals, P < 0.001). Conclusion The fact that CPM⁺ ADCs often co-express with EGFR suggests a functional-regulatory link between these proteins which might have therapeutical consequences. The present novel data could lead to improved IHC tests in lung adenocarcinomas for EGFR expression. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Acute cerebral infarction and extra pontine myelinolysis in children with new onset type 1 diabetes mellitus

Neurological complications of diabetic ketoacidosis (DKA) are still associated with significant mortality and morbidity. We report on two children who suffered from acute cerebral infarction (CI) and extra pontine myelinolysis (EPM) at onset of type 1 diabetes. Initially, clinical management had not been performed according to generally accepted guidelines. Putative risk factors that may have predisposed for the development of acute cerebrovascular complications are discussed. Not only cerebral edema (CE) but also other severe neurological complications such as CI should be suspected when neurological deterioration occurs during DKA. We conclude that not only an exceeded rehydration therapy but also a rapidly reduced serum osmolality due to an unbalanced rapid blood sugar decrease and serum sodium increase may have lead to the neurological disease. We propose that a reserved and well-defined rehydration strategy in the first 6 (-12) h of therapy is crucial for recovery and can reduce neurological complications of patients with DKA.     

Efficient peripheral construction of functional human regulatory CD4(+)CD25(high)Foxp3(+) T cells in NOD/SCID mice grafted with fetal human thymus/liver tissues and CD34(+) cells

Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical regulators of immune tolerance in humans and mice. Mice with humanized immunity have been developed by various transplantation strategies of human tissues or cells related to immunity, which are being extensively applied in biomedical research. However, it is unclear whether human CD4(+)CD25(+) regulatory T cells can normally develop in human thymic grafts and efficiently populate in the periphery in NOD/SCID mouse recipients. In human thymic grafts, high percentage of mature human CD4(+)CD25(high) regulatory T cells was detected. Human CD4(+)CD25(+) regulatory T cells maturing in fetal human thymus grafts could subsequently output to the periphery of NOD/SCID mouse recipients. Importantly, these cells exhibited Foxp3(+)CD45RO(+)CTLA4(+)CD127(-) phenotype, similarly to those in healthy individuals. In addition, human CD4(+)CD25(+) regulatory T cells maturing in human thymic grafts suppressed proliferative response of CD4(+)CD25(-) T cells to allogeneic antigens, though the peripheral CD4(+)CD25(+) regulatory T cells in fetal human thymus-grafted NOD/SCID mice showed somewhat decreased immunosuppressive ability compared with normal CD4(+)CD25(+) regulatory T cells. Thus, this humanized animal model is suitable for examining development and function of human CD4(+)CD25(+) regulatory T cells in vivo.     

浅析中成药治疗儿童骨病的临床合理应用

儿童处于特殊的生理期,骨科疾病多发,但是临床上缺少专门的骨科儿童用药,儿童经常使用成人药物,导致发生不良反应。探析骨科中成药的用药特点,根据《中成药临床应用指导原则》,将骨科儿童用药总结为"重特点、重适量、重避险、重种类、重给药、重短用"6点。结合儿童骨科疾病就医用药的特殊性,就骨科中成药的儿童使用原则进行剖析,为临床上最大程度地避免或减少不良反应的发生、获得最佳疗效提供参考。认为儿童使用骨科中成药应在保证有效性和安全性的前提下,充分衡量风险和收益,制定合理的用药方案。