Impaired monocyte differentiation in children with acute lymphoblastic leukaemia: its evaluation by peroxidase activity and ultrastructure

The ability of monocyte differentiation in childhood acute lymphoblastic leukaemia (ALL) was evaluated on the basis of the ultrastructure and peroxidase (PO) activity which could show the differentiation of cultured monocytes. In the control, PO activity limited to the granules decreased time-dependently during culture for 4 d, and was closely associated with the morphological development to macrophages. In childhood ALL, monocytes showed poor changes in both PO activity and morphological features during culture for 4 d compared to the control. Therefore, we conclude that monocyte to macrophage differentiation is impaired in childhood ALL.     

Kidney dysfunction induced by protein overload nephropathy reduces serum sulfatide levels in mice

We recently proposed serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure (ESRF), based on the possible antithrombotic properties of this molecule. In this earlier study, the level of serum sulfatides was gradually decreased in parallel with kidney dysfunction; however the precise mechanism underlying this decrease was unknown. The aim of the present study was to investigate the mechanism underlying the decrease in serum sulfatide levels caused by kidney dysfunction in an experimental animal model. To produce a kidney dysfunction animal model, we prepared a mouse model of protein overload nephropathy. Using high-throughput analysis combined with matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, we measured the levels of sulfatides in the sera, livers, small intestines and kidneys of protein overload nephropathy mice. As the disease progressed, the levels of sulfatides in sera decreased. Also, the levels in livers and small intestines decreased in a similar manner to those in sera, to approximately 60% of the original levels. On the contrary, those in kidneys increased by approximately 1.4-fold. Our results indicate that kidney dysfunction affects the levels of sulfatides in lipoprotein-producing organs, such as livers and small intestines, and lowers the levels of sulfatides in sera.     

飞行质谱法测定血清脑硫苷脂

目的建立基质辅助的激光解吸附离子化-飞行时间质谱法（MALDI-TOF—MS）测定血清脑硫苷脂的方法,并探讨人血清参考范围。方法经去蛋白、各种条件的高温皂化、萃取、干燥后的血清,用不同浓度的过滤溶剂在MonoTip C18洗脱管中过滤杂质．以桂皮酸为基质,在飞行质谱仪上点样测定。在优化后的条件下测定方法的线性范围、回收率与人血清参考范围。结果用90％甲醇配制的浓度0．1mol／LNaOH在150℃皂化25min、用体积比6：4的蒸馏水与甲醇在MonoTip C18管过滤杂质效果最好。方法线性范围为浓度0—20nmol／ml,回收率为73．7％-75．5％,40例健康人血清参考范围：浓度（8．2±1．5）nmol／ml,男女间差异无统计学意义（P〉0．05）。结论通过飞行质谱仪测定血清脑硫苷脂的含量,具有较高的准确性和线性范围。     

Expression of cathepsin D and B in invasion and metastasis of squamous cell carcinoma

To determine the involvement of proteinases with hydrolytic activity towards extracellular matrix and basement membrane, in invasion and metastasis of tumour cells, the expression of cathepsin D, an aspartic proteinase, and cathepsin B, a cysteine proteinase, was studied. Formalin-fixed paraffinembedded specimens from 13 patients who had squamous cell carcinomas (SCC) with local recurrence, skin and/or lymph node metastasis were examined. Cathepsin D stained intensely as a granular pattern (mature enzyme) in tumour cells of 69% of primary lesions and all the secondary lesions of the patients with SCC. Cathepsin B stained more intensely in SCC cells of all of the primary and secondary lesions than in normal epidermis: staining patterns were almost diffuse (procathepsin B). Granular and diffuse patterns (mature enzyme of cathepsin D and procathepsin B, respectively) appeared in the outer and inner parts of tumour islands, respectively. The presence of the active mature form of cathepsin D and procathepsin B in metastatic skin lesions of SCC was confirmed by Western blotting analysis. The presence and localization of the active mature form of cathepsin D suggests that activated cathepsin D may be involved in the invasion and metastasis of SCC.     

Short‐term effect of combined drug therapy and cognitive stimulation therapy on the cognitive function of Alzheimer's disease

Background: Acetylcholinesterase inhibitors (i.e. donepezil) are known to benefit Alzheimer's disease (AD) patients. However, the combined effects of acetylcholinesterase and cognitive stimulation therapy (CST) are still debated. The present study examined their combined effects on the progression of cognitive decline in AD. Methods: The present study was a non‐randomized controlled study and included two groups of patients with AD (i.e. CST group and control group). The CST group consisted of 31 patients with AD who received donepezil and weekly, 30‐min CST sessions over the course of 7 weeks. The control group consisted of 18 patients who received only donepezil. Changes in cognitive abilities were assessed with Hasegawa's Dementia Scale‐Revised (HDS‐R) and were statistically analyzed by repeated‐measure analysis of variance (anova ). Results: ANOVA showed a significant group × time interaction effect on the HDS‐R score. HDS‐R scores for the CST group increased significantly during the intervention period, whereas the scores for the control group did not increase. Differences between the means of pre‐ and post‐test HDS‐R scores were significantly different between the groups; scores were significantly higher for the CST group than the control group. The groups differed significantly in the proportion of subjects whose score increased by more than four points on the HDS‐R (Fisher's exact test, P < 0.05; 8 patients (25.8%) in the CST group and none (0.0%) in the control group). Conclusions: These results suggest that CST is one of the important non‐pharmacological treatment strategies for patients with AD.     

Atorvastatin or transgenic expression of TFPI inhibits coagulation initiated by anti‐nonGal IgG binding to porcine aortic endothelial cells

Summary. Background: Intravascular thrombosis remains a barrier to successful xenotransplantation. Tissue factor (TF) expression on porcine aortic endothelial cells (PAECs), which results from their activation by xenoreactive antibodies (Abs) to Galα1,3Gal (Gal) and subsequent complement activation, plays an important role. Objectives: The present study aimed to clarify the role of Abs directed against nonGal antigens in the activation of PAECs to express functional TF and to investigate selected methods of inhibiting TF activity. Methods: PAECs from wild‐type (WT), α1,3‐galactosyltransferase gene‐knockout (GT‐KO) pigs, or pigs transgenic for CD46 or tissue factor pathway inhibitor (TFPI), were incubated with naïve baboon serum (BS) or sensitized BS (with high anti‐nonGal Ab levels). TF activity of PAECs was assessed. Results: Only fresh, but not heat‐inactivated (HI), naïve BS activated WT PAECs to express functional TF. Similarly, PAECs from CD46 pigs were resistant to activation by naïve BS, but not to activation by fresh or HI sensitized BS. HI sensitized BS also activated GT‐KO PAECs to induce TF activity. TF expression on PAECs induced by anti‐nonGal Abs was inhibited if serum was pretreated with (i) an anti‐IgG Fab Ab or (ii) atorvastatin, or (iii) when PAECs were transgenic for TFPI. Conclusions: Anti‐nonGal IgG Abs activated PAECs to induce TF activity through a complement‐independent pathway. This implies that GT‐KO pigs expressing a complement‐regulatory protein may be insufficient to prevent the activation of PAECs. Genetic modification with an ‘anticoagulant’ gene (e.g. TFPI) or a therapeutic approach (e.g. atorvastatin) will be required to prevent coagulation dysregulation after pig‐to‐primate organ transplantation.     

Signet ring cell adenocarcinoma of the urachus

Signet ring cell adenocarcinoma of the urachus is an extremely rare variety of adenocarcinoma of the urachus; only 23 cases have been reported in the literature to date. In the present report we discuss two more cases of this type and review the literature. For our first case, a 17-year-old man was treated with partial cystectomy with en-bloc excision of the urachus and umbilicus. He received local radiotherapy because of positive surgical margins. Local recurrence occurred after 21 months of diagnosis and he was lost to follow up. For our second case, a 31-year-old man was found to have peritoneal carcinomatosis at the time of surgery and partial cystectomy was carried out as a palliative procedure for hematuria. He received six cycles of chemotherapy, a combination of methotrexate, vinblastine, adriamycin and cisplatinum. The patient's response to the chemotherapy lasted for 8 months, after which his disease progressed and he died 19 months after diagnosis.     

A case of Sweet''s syndrome following septic pulmonary emboli after high-dose chemotherapy for advanced testicular cancer

A 33-year-old man with advanced testicular cancer underwent high-dose chemotherapy combined with peripheral blood stem cell transplantation. After administration of granulocyte colony-stimulating factor (G-CSF), multiple infiltrative erythema was identified on the face, thigh, and lower leg. A dermatologist diagnosed this as Sweet's syndrome caused by G-CSF; consequently G-CSF administration was stopped. When the skin lesions had improved, phlebitis was found at the injection site of the peripheral vein catheter. The patient then suffered from sudden left chest pain and dyspnea. Chest computed tomography showed the characteristic findings of septic pulmonary emboli (SPE). He was treated by the administration of vancomycin, fluconazole, and pazufloxacin mesilate. Although Sweet's syndrome and SPE are rare diseases, the presence of these diseases must be considered when performing chemotherapy for urological malignancy.