THE TRYPSIN-INDUCED LEUCOSTASIS WHICH LEADS TO EMPHYSEMA IN THE HAMSTER IS NOT DUE TO CONTAMINATING ENDOTOXINS

Intravenous injection of trypsin in the rat induces early lung leucostasis and emphysema of delayed onset. This report confirms that this emphysema is not rat-specific and that the leucostasis is not related to the presence of contaminating endotoxin in the trypsin. In hamsters ( n =37), leucostasis did not occur when they were injected with heat-treated trypsin, but numerous granulocytes were sequestered in the vessels of hamsters receiving a fresh solution of trypsin. In these hamsters, the number of granulocytes harvested by lavage increased significantly (1·87×10⁶ per ml, P <0·001) compared with hamsters injected with either heat-denatured trypsin (0·89) or saline (0·86), or compared with controls (0·86). Emphysema was inconstantly observed in hamsters 6 or 12 weeks after injection with trypsin for 1 h. It was frequently (17/20) present and always (20/20) well developed (intercept+180 per cent) in the 2-h perfused hamsters whose lungs were abnormally heterogeneous (index+100 per cent) relative to the seven controls and to the nine saline-injected hamsters. The efficiency of trypsin in triggering emphysema (percentage of hamsters having abnormal values of intercept) was dependent on the time of perfusion. This form of experimental emphysema is thus considered to be due to an endotoxin-independent leucostasis.     

脑内注射Aβ_(25-35)未见对大鼠隔-海马胆碱能系统的毒性作用

本文运用ＣｈＡＴ 免疫组织化学方法和ＡＣｈＥ组织化学方法观察了Ａβ２５ ３５对大鼠隔 海马胆碱能系统的影响。结果如下：Ａβ２５ ３５注射入内侧隔核，存活１４ ｄ，内侧隔核ＣｈＡＴ 阳性细胞和其支配靶区海马ＡＣｈＥ 阳性纤维的形态和数量未见明显变化；Ａβ２５ ３５注射入海马，存活１４ ｄ，注射点附近ＡＣｈＥ纤维和同侧内侧隔核ＣｈＡＴ 阳性细胞也未见明显变化。上述结果显示，在目前实验条件下，脑内注射Ａβ２５ ３５对大鼠隔 海马胆碱能系统没有明显影响。结合文献讨论，本文作者认为：Ａβ对中枢胆碱能系统是否具有毒性作用还有待进一步探索。     

DELETION OF THE 3 ′ SPLICE SITE OF THE LEADER-VARIABLE REGION INTRON OF IMMUNOGLOBULIN HEAVY CHAIN GENES INDUCES A DIRECT SPLICING OF LEADER TO CONSTANT REGION,RESULTING IN THE PRODUCTION OF TRUNCATED μ-CHAINS

An Abelson virus-transformed immature B cell line, AT8-1-12-5-2, produced truncated μ-chains. Sequencing analysis of the V_HDJ_H complex on the expressed H-chain allele revealed the deletion of 75 nucleotides that involved leader-variable region intron and the 5’ end of the variable region, which resulted in the loss of the 3′ splice site of leader-variable region intron. Sequence studies of a leader- and C_H1 -containing cDNA clone showed that leader region was directly spliced to the C_H1 exon, resulting in the production of the truncated μ-chains without variable portion. Our results demonstrated for the first time that the only loss of the 3′ splice site of leader-variable region intron could induce an aberrant splicing between leader and constant region.     

C5 DEFICIENCY IN A/J MICE IS NOT ASSOCIATED WITH RESISTANCE TO THE DEVELOPMENT OF SECONDARY AMYLOIDOSIS

The aim of the study was to determine whether C5 deficiency in the mouse is associated with resistance to the development of secondary amyloidosis. Chronic inflammation was induced in the F₂ progeny, derived from matings between amyloid-susceptible and amyloid-resistance mice, by daily injections of azocasein for thirty days. Using a restriction fragment length polymorphism generated by digestion of genomic DNA with the restriction enzyme HindIII, C5 sufficient and deficient DNA can be clearly differentiated. Eight mice were found to be C5 sufficient, 32 were heterozygotes and 14 were found to be C5 deficient. Grading of the splenic amyloid load from negative to 4+ was performed after staining tissue squashes with Congo red and viewing them under a polarizing microscope. Seventeen mice were noted to have negative to trace, 18 had moderate (1+-2+) and 19 had heavy (3 H+-4+) amyloid deposition. There was no correlation between splenic amyloid load and C5 deficiency. Based on these results it is clear that C5 deficiency and resistance to secondary amyloidosis are not associated.     

LINKAGE OF NEURAMINIDASE AND α-MANNOSIDASE TO THE MAJOR HISTOCOMPATIBILITY COMPLEX IN THE RAT

Variation in enzyme activity of liver neuraminidase and in electrophoretic mobility of liver α-mannosidase is controlled by a gene or by independently acting genes linked to the major histocompatibility complex of the rat.     

HLA,AND THE RESPONSE TO TREATMENT WITH γ-TYPE ENDORPHINS IN SCHIZOPHRENIA

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with γ-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with γ-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with γ-type endorphins (RR = 24.6, P_uncorr.= 0.0015).Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with γ-type endorphins.     

GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAEMOGLOBIN: I. DEMONSTRATION OF SEPARATE GENETIC CONTROL OF THE RESPONSES TO THE α- AND β-SUBUNITS BY IN VITRO LYMPHOCYTE PROLIFERATION

These studies were undertaken to analyse the genetic control of the immune response to an oligomeric protein and the role of individual subunits in the regulation of the response. Human adult haemoglobin (Hb) was selected as a model for these studies because it is a well-characterized protein and its antigenic structure is being determined in our laboratories. Mice of various congenic strains were immunized with Hb and the lymph node cells from Hb-primed mice were challenged in vitro with Hb, and its α-chain and β-chains as well as an appropriate control antigen. Lymphocyte proliferation was determined by ³H-thymidine incorporation. The data collected indicated that mice of the H-2^b and H-2^d haplotypes were high responders while H-2^k, H-2^s, H-2^q and H-2^j haplotype mice were low responders to Hb. Studies with H-2 recombinant strains indicated that the immune response to Hb and its subunits is determined by genes in the I-A subregion and the D end of the H-2 complex. The significance of these findings in terms of control and regulation of the overall response to native Hb are discussed.     

未折叠蛋白反应对维甲酸诱导鼠胚胎干细胞分化的作用

目的 研究未折叠蛋白反应(UPR)在神经分化过程中的作用。方法 应用全反式维甲酸(RA)诱导鼠胚胎干细胞(ES)，通过免疫细胞化学和RT-PCR方法检测神经组织特异性标志物的表达，建立以RA诱导ES细胞得到的神经分化的初步模型，再分别用RT-PCR和Westem blot方法检测模型中UPR分子的表达。结果 RA诱导后得到大量表达神经特异性标志物的细胞。UPR关键分子Irel α的表达在RA处理组和未经RA处理组中均下降，但未经RA处理组中Irel α的表达始终低于同一时间RA处理组细胞；Grp78的表达在RA处理组随诱导时间延长逐渐上升，但在未经RA处理组Grp78的表达未见上升。Irel α和Grp78的这种表达变化与RA诱导细胞中神经特异性标志物的表达情况相关。结论 以RA诱导ES细胞得到表达神经特异性标志物的细胞分化系统，可作为研究神经发育的初步模型，其模型中UPR分子的表达变化提示，UPR通路可能在神经发育过程中起一定作用。     

压力诱导血管平滑肌细胞整合素β3、桩蛋白和纽蛋白的变化

目的 研究压力对大鼠颈总动脉血管平滑肌细胞整合素β3、桩蛋白和纽蛋白的分布与表达的影响，探讨它们在血管平滑肌细胞的机械应力信号转导中的作用。方法 不同压力(160mmHg和80mmHg)灌流大鼠颈总动脉30min，免疫组织化学和免疫电镜观察整合素β3、桩蛋白和纽蛋白在血管平滑肌细胞上的表达和分布变化。结果 高压和常压灌流对大鼠颈总动脉平滑肌细胞的整合素β3、桩蛋白和纽蛋白的表达无明显影响，但高压使整合素β3、桩蛋白和纽蛋白在平滑肌细胞膜上的分布发生改变，向离管腔面的平滑肌细胞膜聚集。结论 高压诱导了整合素β3、桩蛋白和纽蛋白向离管腔面的平滑肌细胞膜聚集。提示整合素β3、桩蛋白和纽蛋白可能在血管平滑肌细胞的机械应力信号转导中发挥作用。     

不同诱导剂对大鼠骨髓间充质干细胞向神经细胞分化的作用

目的 观察体外不同诱导方法对大鼠骨髓间充质干细胞(MSCs)向神经细胞分化的作用.方法 体外培养、扩增骨髓MSCs,分别采用化学诱导剂(2-巯基乙醇 二甲基亚砜)和生物诱导剂,诱导骨髓MSCs分化为神经细胞.用神经元特异性烯醇化酶(NSE)、神经丝蛋白(NF)和胶质纤维酸性蛋白(GFAP)免疫组织化学方法对诱导后的细胞进行鉴定和诱导率分析.应用组织学方法显示尼氏体.结果 倒置显微镜下可见,MSCs经两种方法诱导48h后,细胞均向神经细胞分化,胞体呈锥形、多角形,由胞体伸出较长的轴突样和树突样突起,且有分支.免疫组织化学鉴定显示,诱导后的细胞能特异性表达NSE、NF,不表达GFAP.化学诱导剂组NSE阳性细胞率为86.9%,NF阳性细胞率为85.6%;生物诱导剂组NSE阳性细胞率为88.2%,NF阳性细胞率为86.8%,两组间无显著差异(P＞0.05).硫堇-伊红染色显示胞体内有大量的尼氏体.结论 体外两种诱导方法均可诱导大鼠骨髓MSCs分化为神经细胞.     

EXPRESSION OF THE LAMININ γ2 CHAIN IN PANCREATIC ADENOCARCINOMA

Forty-two pancreatic adenocarcinomas were investigated immunohistochemically and by in situ hybridization for the expression of the laminin γ 2 chain. In 41 cases, intracytoplasmic immunoreactivity for the γ2 chain was seen. Positive tumour cells were located especially at the epithelial–stromal interface of the tumour cell islands. In 22 cases, diffuse laminin γ2 chain immunoreactivity could also be seen in stroma and in seven cases, occasional positivity was detected in the neoplastic basement membranes. Signals for laminin γ2 chain mRNA in tumour cells displayed a distribution similar to that observed on immunohistochemistry. There were significantly more cases with less than 20 per cent of laminin γ2 chain-positive tumour cells in tumours extending to peripancreatic tissues and/or tumours with regional or distant metastases ( P =0·029). A corresponding statistical significance could also be noted in the mRNA level ( P =0·025). The results show that pancreatic adenocarcinomas display a high activity of laminin γ 2 chain synthesis. Tumours with a strong laminin γ2 chain synthesis show a lower invasive and metastatic potential than tumours with a weak or moderate laminin γ2 chain expression.     

THE THERAPIST AND THE FOOL: AN EXPLORATION OF WHY SOME PATIENTS ATTEND THERAPY IN ORDER TO NOT BE HELPED

ABSTRACT The writer considers why some patients present an apparent commitment to the work of therapy, through regular and reliable attendance at sessions, whilst seeming to disregard or attack anything of value in the therapy. He finds some answers in Shakespeare's King Lear . The therapist, whilst being abused, like the Fool in Lear, is providing an essential management of a split which enables the patient to feel neither narcissistic pain nor dependency anxiety.     

ACETYL CHOLINESTERASE IS EXPRESSED IN THE FOLLICULAR DENDRITIC CELLS OF GERMINAL CENTRES: DIFFERENCES BETWEEN NORMAL AND NEOPLASTIC FOLLICLES

Acetyl cholinesterase (AcChE) was demonstrated by histochemistry in the follicular dendritic cells (FDCs) of the germinal centres of lymph nodes, tonsils, and bowel lymphoid tissue. Its presence in the FDCs was confirmed by double immunostaining for CD21 or DRC-1. AcChE-positive FDCs are concentrated in the inner portion of the light zone of the germinal centre, being absent from the dark zone. In the lymphoid tissue surrounding the germinal centres are AcChE-positive blood vessels; double staining shows that the AcChE is present in the pericytes surrounding the endothelium of the blood vessels. In contrast to the reactive follicle, the AcChE reactivity in FDCs of follicle centre lymphoma is absent or minimally expressed, although the dense FDC mesh is well stained with CD21 or DRC-1. This suggests that the AcChE is not constitutively expressed in FDCs but that its expression is influenced by the state and activity of the lymphoid cells in the germinal centre. The reduced level of AcChE staining can be profitably employed in the diagnosis of follicle centre lymphoma.     

单抗免疫导向药物3Al—DM对CFU—GM的效应试验

应用抗Ｔ淋巴细胞单抗（ＭｃＡｂ）３Ａｌ－柔霉素（ＤＭ）免疫结合物，在体外对骨髓粒－单核细胞集落形成单位（ＣＦＵ－ＧＭ）进行导向杀伤效应试验。结果与Ｂ细胞单抗－ＤＭ结合物十分近似。说明单抗３Ａｌ－ＤＭ对ＣＦＵ－ＧＭ没有影响，不损伤正常骨髓造血干细胞，为３Ａｌ－ＤＭ用于体外骨髓净化提供实验依据。     

GLUT3阳性神经细胞在大鼠脑中的分布及其与脑内葡萄糖监控系统的关系

本文利用抗ＧＬＵＴ３ Ｃ－末端部分合成肽的抗血清对大鼠脑中ＧＬＵＴ３ 阳性神经细胞的分布进行了免疫组织化学研究。结果表明,除在大脑皮层的广泛区域和海马ＣＡ 区存在大量的ＧＬＵＴ３ 阳性神经元外,皮层下的某些核团和区域的神经元以及第三脑室腹侧部的ｔａｎｙｃｙｔｅ 也表达丰富的ＧＬＵＴ３ 蛋白。有趣的是,这些核团的大部分参与构成脑内葡萄糖监控系统的神经网络,有些阳性细胞（如下丘脑外侧区,黑质的神经元和ｔａｎｙｃｙｔｅ ）是这一网络中对血液和脑脊液中葡萄糖浓度发生反应的化学敏感细胞。这一新发现提示ＧＬＵＴ３ 可能与血糖浓度的神经调控有关。