Effects of zymosan-activated plasma and phorbol myristate acetate on isolated, perfused rabbit lungs

The effects of complement activation on pulmonary vascular permeability are disputed. In rabbit lungs perfused with autologous blood, zymosan activated plasma (ZAP) induced a moderate increase in pulmonary vascular resistance (PVR), but did not detectably change the vascular permeability within 2 h. The stronger neutrophil granulocyte (PMN) activator, phorbol myristate acetate (PMA), usually gave larger PVR increases and also increased pulmonary vascular permeability. Lungs from neutropenic animals, similarly perfused and given PMA, showed unchanged PVR reactions but had no apparent increase in vascular permeability. Lungs perfused with cell-free medium and given PMA displayed modest PVR increases, and no measurable permeability change. The lung preparatory procedure itself markedly influenced leukocyte circulation. Exsanguination of lung donors decreased the concentration of circulating PMN significantly, and they virtually disappeared from the perfusate within minutes after start of lung perfusion. PMN-mediated effects must therefore have been caused by cells already sequestered in the lungs. We conclude that ZAP does not induce an increased pulmonary vascular permeability in isolated, perfused rabbit lungs, in contrast to PMA. The permeability effects of PMA appear to be PMN dependent.     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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Human myeloma light chains with increased molecular weight: high frequency among lambda chains

The discovery of a human myeloma protein comprising a kappa L-chain with an increased mol. wt of 30,000) (Bouvet et. al., 1980) prompted investigations on the incidence of such heavier L-chains among other human myeloma proteins. In 105 samples examined, 34 were found to have L-chains heavier than normal (23,000-24,000), ranging from 25,000 up to 31,000, and five of lighter mol. wt (21,000-22,000). These mol. wt abnormalities were detected by electrophoresis in sodium dodecyl sulfate 10% polyacrylamide gels (SDS-PAGE) after reduction with 2-mercaptoethanol. The mol. wt of three of the heavier kappa or lambda chains was also estimated by filtration through a Sephadex G100 column and by sedimentation equilibrium. All three methods indicated a mol. wt increase of about 15-25% as compared with the usual mol. wt. The distribution of the high mol. wt chains among all L-chains examined was found to be 11 out of 62 kappa chains (17.7%) and 23 out of 43 lambda chains (53%) (P less than 0.001). A preferential association of such L-chains with H-chains producing multiple bands in SDS-PAGE (P less than 0.01) and an association between multiple L-chain and multiple H-chain band (P less than 0.05) were also observed. In contrast, no abnormal L-chain was found in immunoglobulins from normal subjects. Spontaneous degradation of the normal H-chains sometimes yielded fragments of 30,000 mol. wt. These fragments were easily distinguishable from abnormal L-chains. The nature of extra mol. wt in heavy L-chains was investigated for the presence of carbohydrate moiety. Four large and three normal size L-chains were examined for amino-sugar and sialic acid content. A small amount (one residue per molecule) of amino-sugar was detected only in two normal and two heavy L-chains, whereas sialic acid was only found in the heaviest (27,000-30,000) L-chains (Lh) and in small percentage (one or two residues per molecule). Total sugar estimation in one Lh chain indicated a proportion not exceeding three or four residues per L-chain (mol. wt 1,000) and this is insufficient to explain the 15-25% (3,600-6,000) mol. wt increase. It is therefore possible that, at least in some heavy myeloma L-chains, an additional peptide is expressed. Whatever the nature of the increase it would be of interest to elucidate whether this is a marker of malignant process or of an intermediate step of normal Ig synthesis.     

Insecticide and fungicide effect on thermal and olfactory behavior of bees and their disappearance in bees’ tissues

Plant protection products may affect the behavior of organisms which are not a target of control. The effect of Karate Zeon 050 CS (λ-Cyhalothrin -based insecticide; λ-CBI) and Amistar 250 SC (Azoxystrobin-based fungicide; ABF) was determined on Apis mellifera worker attraction towards their own colony odour, along with temperature preferences. Bees exposed to pesticides prefer the environment with the odour of their nest less often than the control group, and that insecticide-treated bees chose warmer environments than the control insects. The observed differences in the bees, especially with attraction towards their own colony, were dependent on the time of day. Chromatographic analyses indicated that λ-Cyhalothrin elimination was half that of Azoxystrobin in bee organisms, and both agents retarded each other’s clearance. Mathematical modeling estimated that despite a relatively high disappearance rate, both compounds might have been bio-accumulated at relatively high level.     

慢性乙型肝炎患者降钙素基因相关肽和α-干扰素-λ4基因多态性对α-干扰素治疗应答的影响*

目的 探讨慢性乙型肝炎(CHB)患者血清降钙素基因相关肽(CGRP)和α-干扰素-λ4(IFNL4)基因多态性对α-干扰素治疗应答的影响。方法 2018年9月～2021年2月我院诊治的CHB患者92例,给予所有患者α-干扰素α-2b治疗1年。采用聚合酶链反应-限制性片段长度多态性检测血CGRP基因rs155209位点及IFNL4基因rs368234815和rs12979860位点多态性,应用Logistic回归分析基因多态性与α-干扰素治疗应答的关系。结果 在治疗1年末,本组应答67例(72.8%),未获得完全应答25例(27.2%);非应答组CGRP-rs155209位点CC基因型和等位基因C比率分别为36.0%和56.0%,显著高于应答组的16.4%和32.8%(P＜0.05);非应答组IFNL4-rs368234815位点TT/TT基因型和TT基因频率分别为76.0%和86.0%,显著低于应答组的92.5%和95.5%(P＜0.05);非应答组IFNL4-rs12979860位点CC、CT和TT基因型比率分别为44.0%、44.0%和12.0%,与应答组的40.3%、46.3%和13.4%比,无显著性差异(P＞0.05);应用非条件Logistic回归模型计算校正性别和年龄,结果显示CGRP-rs155209位点CC基因型是影响治疗无应答的危险基因型【OR值为1.489(95%CI:1.103～2.009)】,而IFNL4-rs368234815位点TT/TT 基因型是α-干扰素治疗应答的保护基因型【OR值为0.652(95%CI:0.477～0.893)】。结论 CGRP基因rs155209位点CC基因型是接受α-干扰素治疗CHB患者可能无应答的危险基因型,而IFNL4基因rs368234815 位点TT/TT 基因型可能是治疗应答的保护基因型,将影响CHB患者对α-干扰素治疗的生化和病毒学应答反应。     

Influence of tissue fixation on the microextraction and identification of amyloid proteins

In surgical pathology, correct immunohistochemical identification of AL amyloidosis poses a particular problem. Immunostaining for lambda- or kappa-light chains is commonly encountered even in non-immunoglobulin-derived amyloidoses, which leads to a false-positive classification as AL amyloidosis. In this respect, microextraction of amyloid proteins from surgical pathology specimens and their subsequent biochemical characterization may prove useful in reaching the correct diagnosis. In this study, we investigated systematically the influence of fixation on the extraction of amyloid proteins from amyloid-containing tissue samples. Tissue samples were obtained from a patient with generalized AA amyloidosis and from a second patient with generalized AL amyloidosis. The samples were stored either unfixed or fixed in phosphate buffered 4% p-formaldehyde, methacarn, or Bouin for 3 days, 1 week, or 1 month. Thereafter, proteins were extracted according to the procedure of Layfield et al, separated by SDS-PAGE and subjected to Western blotting, using antibodies directed against AA amyloid and immunoglobulin-derived lambda-light chain. Following this procedure, a variety of differently sized AA amyloid or lambda-light chain immunoreactive protein bands were found in both patients, which is typical for amyloid proteins. Fixation time did not per se prohibit the extraction of these amyloid proteins from tissue samples, which remained detectable irrespective of fixation time. Although all three fixatives impaired the resolution of some, but not all, individual amyloid proteins, this procedure may help to confirm or reject a diagnosis of AL amyloidosis, because detection of several lambda- or kappa-light chain immunoreactive protein bands in the low-molecular-weight range (<20 kDa) is a common characteristic of their amyloid nature.     

Immunoglobulin D-λ/λ biclonal multiple myeloma: A case report

BACKGROUNDImmunoglobulin D (IgD) multiple myeloma (MM) is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System (ISS) when admitted. As a special type of IgD myeloma, IgD-λ/λ biclonal MM is rarer. Its serum protein electrophoresis and serum immuno-fixation electrophoresis (IFE) might find no anomalies even if the bone marrow (BM) examination is performed. Thus, it is easy to miss the diagnosis.CASE SUMMARYA 62-year-old man diagnosed as IgD-λ/λ myeloma (ISS stage III) was admitted with fatigue and weight loss. The physical examination suggested an anemic face, a few moist rales at the left lung base, and mild concave edema in both lower extremities. Laboratory examinations showed the elevated creatinine levels, β2-microglobulin, lactic dehydrogenase, and erythrocyte sedimentation rate, while the decreased neutrophils, granulocytes, and hemoglobin. In the serum protein electrophoresis, there appeared two inconspicuous M-spikes. Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands in λ region, but only one corresponding heavy chain band in the antisera to IgD region. The BM histology and BM cytology both supported the diagnosis of IgD-λ/λ myeloma.CONCLUSIONThis case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λ myeloma to help minimize the chance of misdiagnosis.     

干扰素λ的药理学及临床应用研究进展

干扰素λ（IFN-λ）为一类新发现的Ⅲ型干扰素,隶属于Ⅱ型细胞因子家族,其异二聚体功能性受体复合物IL-28Rα/IL-10Rβ具有组织学分布特异性。IFN-λ主要通过JAK-STAT途径发挥其药理学活性,包括抗病毒、抗增殖及免疫调节作用。在Ⅰ期及Ⅱ期临床试验中IFN-λ产生的不良反应较IFN-α为少,因此在治疗肝炎及特异性抗肿瘤方面可能具有良好的应用前景。本文主要针对近年来IFN-λ的药理学活性及临床应用进行总结。