Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity

Abstract The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-tage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamidc substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.     

Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and CRMP-5 autoantibody.

The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5 immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is usually associated with small-cell lung carcinoma or thymoma. We report on details of a movement disorder that followed anti-B-cell therapy in a patient with lymphoma, and was accompanied by CRMP-5 IgG.     

单项抗HBc阳性的临床分析

临床上对于乙型肝炎的诊断主要是依据病人的 HBV- M结果进行判断 ,对于单项抗 HBc阳性的临床意义 ,目前有不同的争议。通过在临床工作中搜集整理的有关资料进行总结分析 ,认为单项抗 HBc阳性的意义与其在血清中的滴度有关。     

Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Use of the 90Sr applicator for intraoperative radiation therapy in a mouse tumor model

Intraoperative radiation therapy (IORT) research is limited by the lack of small-animal models. We have implanted B16 melanoma into mouse kidneys, which we subsequently operated upon and irradiated with beta rays from a ⁹⁰Sr ophthalmic applicator. The IORT has effectively prolonged survival and produced some cures. The strategy should be applicable to other murine tumors and to other internal implantation sites.     

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.     

异氟醚控制性降压对颅内动脉瘤夹闭术血中S100B含量的影响

目的　测定颅内动脉瘤夹闭前后血中S1 0 0B蛋白含量 ,研究异氟醚控制性降压对脑功能的影响。方法　择期颅内动脉瘤夹闭术病人 30例 ,ASAⅠ～Ⅱ级 ,随机分为两组 :异氟醚降压组 (n=1 5 )和异氟醚非降压组 (n =1 5 )。非降压组术中吸入 1MAC异氟醚维持麻醉。降压组行异氟醚控制性降压 ,平均动脉压下降幅度 30 %～ 4 0 % ,夹闭动脉瘤后降低异氟醚吸入浓度 ,终止降压。分别于切皮前、动脉瘤夹闭后即刻、2、4h、术后第 1、2天取血测定S1 0 0B蛋白含量 ,并于术后 1周随访病人 ,记录有无术后神经系统并发症。结果　 (1 )异氟醚降压后 30min平均动脉压由诱导前的 (95 2± 1 2 3)mmHg降至 (5 8 8± 5 4 )mmHg ,停止降压后 30min血压回升至 (75 1± 8 3)mmHg。降压后外周血管阻力及心肌收缩加速度下降 ,但心率及心输出量均无显著性变化 ;(2 )异氟醚降压组与非降压组间同一时间点血中S1 0 0B蛋白浓度无明显差异。降压组术后第 1天及第 2天血中S1 0 0B蛋白浓度均显著升高 (F =2 94 4 ,P =0 0 1 8)。结论　在颅内动脉瘤夹闭术中应用异氟醚控制性降压可能加重了术后脑损伤 ,不利于病人围麻醉期脑功能的保护     

Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.     

An Unusual Form of Skin Tuberculosis Following B.C.G. Vaccination

A 25-year-old female has had brown to erythematous telangiectatic patches and grouped papules on her face, neck, arm, and trunk since childhood following B.C.G. vaccination. Histopathologically, the lesions consisted of hyperkeratosis, slight acanthosis, tuberculoid granulomas with some Langerhans type giant cells in the mid-dermis. Although various forms of cutaneous tuberculosis after B.C.G. vaccination have been reported, it was difficult for us to assign the patient's skin lesion to any specific disease entity. Remission of her cutaneous lesions occurred clinically and histopathologically after treatment with isoniazid and rifampin.