Experimental columnar metaplasia in the canine oesophagus

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.     

Direct effects of endotoxin on hepatocytes. Synthesis of a specific secretory protein

The synthesis of acute-phase proteins by the liver during sepsis has been thought to be induced primarily by monokines released from activated macrophages, although glucocorticoid hormones may also stimulate this process to a lesser degree. According to this concept, synthesis of these proteins following administration of bacterial endotoxins would be an indirect effect and would not reflect a direct interaction of the endotoxin molecule with the hepatic parenchymal cell. We observed, however, that the synthesis of a 23-kilodalton protein was stimulated directly by the addition of lipopolysaccharide to cultures of primary mouse hepatocytes. The synthesis of this protein was also stimulated by glucocorticoids and interleukin 1. These findings demonstrate that certain hepatic proteins are subject to complex regulation by several factors thought to be important mediators of sepsis; in addition, they suggest that hepatic parenchymal cells may have the intrinsic capacity to respond directly to bacterial endotoxins.     

Bronchoscopy for aspirated foreign bodies in children. Experience in 131 cases

One hundred thirty-one children underwent rigid bronchoscopy under general anesthesia for suspected aspirated foreign bodies. There were 79 boys and 52 girls, with a mean age of 2.1 years. Physical examination showed decreased breath sounds (n = 130) and wheezing (n = 119) over the affected site. Chest roentgenograms were diagnostic or suggestive of aspirated foreign bodies in 127 cases (97%). Radiopaque lesions were noted on roentgenograms in ten cases. Four infants had a preoperative hypoxic arrest. Two patients had negative results of bronchoscopy (1.5%). Extraction of the aspirated foreign body was carried out at laryngoscopy in two patients and by forceps under direct vision at bronchoscopy in 97 patients. A Fogarty catheter was used in 12 cases. Postendoscopic complications included fever (n = 27), pulmonary infiltrate (n = 11), ventilatory support (n = 4), and pneumothorax (n = 2). Rigid bronchoscopy for aspirated foreign body in children is a safe, effective, and sometimes life-saving procedure. Morbidity is low and mortality is zero.     

Effect of interleukin 2 on Kupffer cell activation. Interleukin 2 primes and activates Kupffer cells to suppress hepatocyte protein synthesis in vitro

Interleukin 2 (IL-2) is an essential mediator of the immune response and has also been shown to be protective in experimental models of sepsis. Macrophages have IL-2 receptors but their function is unknown. We investigated the effect of IL-2 on Kupffer cells, the fixed macrophages of the liver, using an in vitro rat hepatocyte-Kupffer cell coculture system. In this model, endotoxin (lipopolysaccharide) triggers Kupffer cells to induce suppression of hepatocyte protein synthesis. We found that pretreatment with 10 U/mL or more of IL-2 primed Kupffer cells, significantly reducing the concentration of lipopolysaccharide necessary to trigger Kupffer cell-mediated suppression of hepatocyte protein synthesis. Higher concentrations of IL-2 (greater than or equal to 1 x 10(4) U/mL) alone were capable of priming and triggering Kupffer cells to suppress hepatocyte protein synthesis. These data show that IL-2 increases Kupffer cell sensitivity to endotoxin, suggesting that IL-2 may play an important role in regulating macrophage responses to septic stimuli.     

聚氨酯避孕套临床前使用可行性和可接受性分析

目的 对使用新型聚氨酯(Pu)男用避孕套的可行性和可接受性进行初步观察。方法 对30对健康已婚夫妇为期6周360次使用国产PU避孕套的效果进行问卷调查。结果 避孕套总破裂率(临床破裂 非临床破裂)为2．22％，临床滑脱率为16．5％，使用观察期间无意外妊娠发生。结论 新型PU避孕套的破裂率和滑脱率分别相近于和高于报道的乳胶避孕套使用情况，感官指标反映PU避孕套具有良好的可接受性。     

Investigating the role of heparin sulfate proteoglycans in hereditary multiple exostoses (HME) tumourigenesis

Introduction Heparin sulfate (HS) has long been implicated in the bone deformity hereditary multiple exostoses (HME), and it is now clear that HME is associated with mutations in the HS biosynthetic genes EXT1 and EXT2. Interestingly, HME is also associated with an increased risk of chondro‐ and osteo‐sarcomas. Methods and results Preliminary analysis of GAG samples purified from fibroblasts of both HME and isolated non‐HME exostoses patients reveal a dramatic shift in the ratio of CS : HS, with the HME and isolated cases having a much higher proportion of CS relative to normal controls. This is true in the case of both shed and cell surface material but is far more extreme in the latter, with the HS reducing from approximately 45% in the controls to less than 10% in HME patients. Initial analysis also reveals shortened chain length within these samples; indeed they often have two populations of chains present. Simple analysis of the total disaccharide composition of these samples demonstrates no significant differences against controls. However, detailed analysis of the subpopulations of chains (as determined by chain length) within these samples as well as cartilaginous samples from exostoses patients may provide further insight into the changes that occur within the biosynthetic pathway following disrupted EXT function. We are also carrying out immunocytochemistry with a variety of HS‐specific antibodies with the aim to further investigate normal HS structure and localization. This is being carried out on human primary chondrocytes isolated from normal patients and also adult mesenchymal stem cells as they undergo differentiation into chondrocytes. HS has been identified in both these cell types, and it is hoped that the manipulation of these cells through RNAi of different enzymes of the HS biosynthetic pathway will provide a suitable model for studying what changes may occur in cellular HS structures over the initial differentiation process in the growth plate. Discussion Together, these investigations should provide a good model to allow us to determine the role of HS in chondrocyte differentiation and maturation in both normal and diseased states.     

中国男性原发不育的遗传高风险因子:Y染色体DAZ基因拷贝缺失

目的 探讨Y染色体无精症因子C区(azoospermia factor C，AZFe)无精症缺失基因(deleted-in-azoospermia，DAZ)家族基因拷贝缺失与中国男性原发不育之间的关系。方法 运用多重PCR与PCR-RFLP检测技术，对210例已生育男性、216例原发无精症与189例严重少精症患者Y染色体AzFc区域DAZ基因家族的基因拷贝数进行分析。结果 在所有已生育男性中未检出DAZ基因拷贝的完全或部分缺失，而在原发无精症与严重少精症患者中DAZ基因拷贝完全缺失率分别为8．8％和12．2％，DAZ1／DAZ2共缺失率分别为8．3％和5．3％。结论 在中国男性原发无精症与严重少精症患者中存在较高频率的DAZ基因拷贝缺失现象，提示Y染色体AZFc区域DAZ基因家族基因拷贝的完全与部分缺失是中国男性原发不育的遗传高风险因子。     

Gaucher disease: abdominal MR imaging findings in 46 patients.

Abdominal magnetic resonance imaging findings were reviewed in 46 patients with Gaucher disease. All patients had hepatosplenomegaly at the time of initial imaging. Splenic nodules were present in 14 patients (30%) and varied in signal intensity. These nodules were isointense on T1-weighted and hypointense on T2-weighted images. Splenic infarcts were seen in 15 patients (33%), and four of these patients (9%) also had subcapsular fluid collections. Both nodules and infarcts were present in the spleen in four patients (9%). Pathologic correlation was performed with specimens from two patients who underwent partial splenectomy. Focal areas of abnormal signal intensity were noted in the liver in nine patients (20%). They were either stellate or segmental, and may represent fibrotic septa with ischemic changes associated with aggregates of Gaucher cells. No changes were noted in the kidneys or abdominal lymph nodes.     

Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice.

Spatial learning in rodents requires normal functioning of hippocampal and cortical structures. Recent data suggest that the cerebellum may also be essential. Neurological mutant mice with dysgenesis of the cerebellum provide useful models to examine the effects of abnormal cerebellar function. Mice with one such mutation, Purkinje cell degeneration (pcd), in which Purkinje cells degenerate between the third and fourth postnatal weeks, were evaluated for performance of spatial navigation learning and visual guidance learning in the Morris maze swim-escape task. Unaffected littermates and C57BL/6J mice served as controls. Separate groups of pcd and control mice were tested at 30, 50 and 110 days of age. At all ages, pcd mice had severe deficits in distal-cue (spatial) navigation, failing to decrease path lengths over training and failing to express appropriate spatial biases on probe trials. On the proximal-cue (visual guidance) task, whenever performance differences between groups did occur, they were limited to the initial trials. The ability of the pcd mice to perform the proximal-cue but not the distal-cue task indicates that the massive spatial navigation deficit was not due simply to motor dysfunction. Histological evaluations confirmed that the pcd mutation resulted in Purkinje cell loss without significant depletion of cells in the hippocampal formation. These data provide further evidence that the cerebellum is vital for the expression of behavior directed by spatial cognitive processes.