Is chronic inflammatory change in the prostate the major cause of rising serum prostate‐specific antigen in patients with clinical suspicion of prostate cancer?

AIM: To evaluate the cause of elevated prostate-specific antigen (PSA) in patients with transrectal needle biopsy negative for prostate cancer. METHODS: Serum PSA concentration, prostate volume, and pathologic findings were examined in 223 patients with negative biopsy for prostate cancer. The degree of prostate inflammation was determined by the extent and degree of inflammation shown by biopsy specimens and is expressed as an inflammation score (range: 0-36). RESULTS: A significant correlation was found between PSA concentration and prostate total volume (P=0.0001). Prostate chronic inflammation showed no correlation with PSA concentration (P=0.485, F=0.488). After allocating patients to normal PSA (4 ng/mL) groups, we found that serum PSA concentrations in both groups were predominantly affected by prostate total volume. CONCLUSIONS: An increase in prostate volume appears to be the major contributor to a high serum PSA concentration in patients with negative biopsy for prostate cancer. However, in contrast to previous reports, there was no correlation between the degree of prostate chronic inflammation and serum PSA concentrations.     

IgE antibodies to protein and mannan antigens of pityrosporum ovale in atopic dermatitis patients

Background Pityrosporum ovale is a common saprophyte on the skin capable of inducing IgE antibody production in atopic dermatitis (AD) patients. Allergens ofP. ovale have been examined in several studies, but consensus on them is lacking. Objective This study was carried out to obtain more information about the IgE antibody response against P. ovale. including niunnun. Methods Sera from 64 AD patients and 10 healthy controls were analysed with immuno-blotting and the nitrocellulose radio allergosorbent test (RAST) method specifically developed to detect antimannan P. ovale IgE antibodies. Results In immunoblotting a total of 39 different IgE stained protein bands were seen. A high molecular weight staining was also seen especially in patients who displayed elevated mannan P. ovale RAST values. The most commonly stained protein bands in immunoblotting were 9 and 96 kD bands with antibodies in 73 and 65% of AD patients who had been positive in commercial P. orbiculare RAST with total serum IgE less than 4000 kU/I. Mannan RAST appeared positive in 77% of them. Positive immunoblotting to either of these bands was seen in 90% and, if added with staining with ihe 20 kD band, in 100% of these AD patients. A comhination of 9 kD IgE staining and mannan P. ovale RAST was positive in 92% of the patients and % kD and mannan P. ovale RAST in 85% of the patients. Conclusion It is evident that P. ovale has several allergens, the 9. 96 and 20 kD regions being the most important. According to our results mannan is also an important allegen of P. ovale     

Chemical shift differences between free and Fab-bound peptide correlate with a two-stage selection of peptide sequences from a random phage display library to delineate critical and non-critical residues for antibody recognition

Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH₂ (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH₂ (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with ¹⁵N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995.     

抗淋球菌IgA蛋白酶单克隆抗体特性的初步研究

本文对以重组淋球菌ＩｇＡ蛋白酶为抗原制备的７株特异性ＭｃＡｂ的特性进行了初步研究。结果有５株（１Ｃ８、１Ｅ５、１Ｆ１１、１Ｇ３和２Ｅ６）能中和淋球菌ＩｇＡ蛋白酶活性。经相加试验初步证明，其中１Ｆ１１、２Ｇ３与其它３株ＭｃＡｂ的作用位点不同。因此，淋球菌ＩｇＡ蛋白酶至少存在３个中和表位。     

Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti-γGT monoclonal antibody 138H11

Aims : Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas. Methods and results : Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma-glutamyltransferase (γGT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin-embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain γGT in paraffin-embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11. Conclusions : The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.     

重症肌无力中枢神经系统受损模型

目的近年研究结果表明，重症肌无力（ＭＧ）病变部位并不仅仅局限于神经肌接头（ＮＭＪ）处突触后膜烟碱型乙酰胆碱受体（ｎＡＣｈＲ），烟碱型乙酰胆碱受体抗体（ＡＣｈＲ－ａｂ）病理作用可能波及到中枢神经系统（ＣＮＳ）。因此，有必要建立模拟ＭＧ患者ＣＮＳ损害的动物模型，研究ＭＧ患者脑脊液中存在的ＡＣｈＲ－ａｂ引起ＣＮＳ损害的机制。方法从ＭＧ患者血中提取的ＡＣｈＲ－ａｂ经侧脑室穿刺注入到大鼠脑室系统，然后观察其症状和体征，以及用脑干听觉诱发电位仪（ＢＡＥＰ）检测鼠脑干听觉传导中枢功能。用免疫组化法（ＡＢＣ）研究ＡＣｈＲ－ａｂ与ＣＮＳ神经－ｎＡＣｈＲ之间免疫结合反应及其分布。结果大鼠除了出现脑干听觉传导中枢功能障碍外，还出现类似于ＭＧ动物模型表现的症状。免疫组化研究结果显示，神经－ｎＡＣｈＲ样阳性免疫反应广泛分布于ＣＮＳ许多部位。结论脑室内注入的ＡＣｈＲ－ａｂ与神经－ＡＣｈＲ结合引起ＣＮＳ功能障碍和出现ＭＧ动物模型样症状。我们首次建立的中枢受损的ＭＧ模型将有助于阐明ＡＣｈＲ－ａｂ引起中枢受损和ＣＮＳ下位运动神经元引起横纹肌收缩无力的机制。     

REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART

1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P₂, such that the majority of InsP isomers derive from Ins(1,4,5)P₃. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.     

Role of immune complexes in thyroid diseases

Institute of Biochemistry, Academy of Sciences of the Uzbek SSR, Tashkent. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. A. Pankov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 168–170, February, 1992.