FREE ANTIGEN AND ANTIBODY CIRCULATING TOGETHER IN LARGE AMOUNTS (HEMAGGLUTININ AND AGGLUTINOGEN IN THE BLOOD OF TRANSFUSED RABBITS)

In rabbits transfused almost daily with the whole citrated blood of other rabbits, an extraordinary condition often develops, which manifests itself in an almost immediate clumping together of all the red cells in specimens of the shed blood. This clumping is due to one or more true agglutinins, of which the strength may be such as to cause clumping in a 1: 2,800 plasma dilution. The agglutinating principle circulates with the corpuscles against which it is effective; but under ordinary circumstances intravascular clumping fails to occur because the union of antigen and antibody can take place only at a temperature several degrees below that of the body. If the temperature is sufficiently lowered, as when a tourniquet is applied to the rabbit''s ear, intravascular clumping ensues. In defibrinated blood, gradually cooled, clumping is first noted as the temperature of 35°C. is approached; and at room temperature (22°) the corpuscles will often come together in a short time into a single, solid mass. At 0°C. the agglutination is still more marked. The reaction seems to be completely reversible, for when the blood is warmed again, the clumps break up and disappear at between 35° and 36°C. Cooling and warming with the resultant clumping and dissociation can be carried out many times on the same blood specimen without apparent change in the corpuscles or in the rapidity of the reaction. The response to temperature changes is extremely prompt. Once it has been elicited, the agglutinating principle may persist for a long time after the transfusions are stopped, in one instance it was still strong 133 days after the last transfusion. During this period the plethora was succeeded by a severe anemia, which in turn was recovered from. In many rabbits no agglutinin develops, and a continuance of the transfusions will not elicit it. Indeed, when present it tends to disappear if the transfusions are persisted in. In several of the animals in which the agglutinin was strongest, the plethora was suddenly succeeded by severe anemia, despite continued transfusions. The character of the temperature control of the agglutination, which somewhat resembles that of the hemolysin in paroxysmal hemoglobinuria, has led us to consider whether the blood destruction might not be due to accidental chilling of the animal. Efforts to induce a fall in the hemoglobin by placing the rabbit''s ear in ice water have as yet been unsuccessful. Thus far no adequate search for an hemolysin has been made. The object of the present paper has been to describe a condition in which large amounts of free antigen and antibody circulate together in the organism, and to demonstrate the factor which prevents their union, the results of which could easily be fatal. The causes of the condition will be dealt with in a subsequent communication.     

THE METABOLISM OF COPPER AND IRON IN SPLENECTOMIZED RATS FREE FROM BARTONELLA MURIS INFECTION

Removal of the spleen in albino rats free from Bartonella muris infection is followed by an increased elimination of copper in the feces, which commences 2 weeks after splenectomy. This is associated with a persistent negative copper balance. An increased retention of iron occurs during a period of 4 to 6 weeks after splenectomy with a return of the iron metabolism to normal after this period. No disturbance in creatine or creatinine metabolism occurs. The uric acid amount is unchanged. There is an increase in the retention of nitrogen, which is first noted 3 weeks after splenectomy. The spleen is essential for the utilization of copper in the body.     

多发性骨髓瘤病人血清游离轻链检测的临床意义

目的探讨血清游离轻链（sFLC）在多发性骨髓瘤（MM）病人诊断、疗效判断中的临床意义。方法应用免疫散射比浊法,测定40例初诊MM病人、30例正常对照及30例IgG型MM病人化疗后不同疾病阶段的sFLC水平。结果初诊MM病人的sFLC水平较正常对照明显异常（t=18.69、18.09,P〈0.01）。IgG型MM病人化疗3个疗程后随着疗效的提高,sFLC浓度逐渐降低（F=558.39、766.59,P〈0.01）。结论应用免疫比浊法测定sFLC对MM诊断和疗效判断有重要价值。     

铜离子加银离子与游离氯协同灭活水中病毒效果的试验观察

铜离子或银离子对水中大肠杆菌噬菌体ｆ２与脊髓灰质炎病毒Ｉ型灭活效果极低。但以４００μｇ／Ｌ铜离子加４０μｇ／Ｌ银离子与０３ｍｇ／Ｌ游离氯协同作用３０ｍｉｎ，则可将两者存活率对数分别减少至４８０６与２６７４，远较单独使用游离氯效果为优。     

EQUILIBRIA IN PRECIPITIN REACTIONS : THE COEXISTENCE OF A SINGLE FREE ANTIGEN AND ITS ANTIBODY IN THE SAME SERUM.

1. In these studies several phases of the predpitm reactions were investigated by the use of purified proteins as antigens. These preparations were edestin from hemp-seed and crystalline ovalbumin from fresh eggs. The ovalbumin, isolated by the method of Hopkins and Pinkus,.was apparently as pure as is obtainable by chemical means. This albumin, however, produced moderately severe anaphylactic reactions in animals sensitized with ovoglobulin. Anaphylactic tests of the individuality of a protein cannot be any longer regarded as the criterion of the purity of the substance as an antigen. Wells and Osborne have shown that proteins of considerable chemical difference may have a common antigenic group which causes mutual anaphylactic reactions in animals sensitized to these proteins. In particular, as egg globulin is a mixture of proteins, one of which is undoubtedly egg albumin, anaphylaxis produced by injections of albumin into animals sensitized to the so called globulin offers no evidence for or against the purity of the albumin. The character of the curves shown in Text-fig. 1 confirms the assumption, based upon chemical data, that crystalline egg albumin is a single protein. 2. With edestin and crystalline egg albumin as antigens phases in the precipitin reaction were found in which these substances and their specific precipitins could be demonstrated to be coexistent but ununited in the same serum. 3. When edestin or crystalline egg albumin is injected into a rabbit immunized thereto, the antigen may be found in the circulating blood during 48 hours after its injection, while at the same time the animal maintains a high titer of free precipitin in its blood. 4. When the pure protein antigen is mixed in proper proportions with the serum of a specifically immunized rabbit and the resulting precipitate removed by centrifugation, the supernatant fluid contains both antigen and antibody. 5. The serum drawn from a rabbit during the period in which free antigen and antibody are coexistent in the circulation undergoes slow spontaneous precipitation when kept in sterile tubes in the ice box. The curve of this reaction is reproduced as Text-fig. 1. The relationships of the parabola indicate that the interaction of antigen and antibody takes place according to a definite law. When sufficient quantitative data are obtained to allow an analysis of this curve, the formulas for this reaction will undoubtedly throw light upon the chemical or physical nature of the process. 6. The protective action of the solution of egg albumin as a third colloid preventing precipitation in a reaction between human serum and its antibody was readily demonstrated. This observation and the constancy of the long prozone in precipitin test with egg albumin are in accord with the protective action of ovalbumin upon colloidal gold.     

关节腔注射臭氧对兔膝骨关节炎模型血浆自由基的影响

目的:通过观察血浆自由基的变化,探讨臭氧对兔膝骨性关节炎(osteoarthritis,OA)的治疗作用及其可能机制。方法:将40只成年新西兰兔随机分为5组,即正常组(A组)、OA组(B组)、20μg/ml臭氧治疗组(C组)、40μg/ml臭氧治疗组(D组)、60μg/ml臭氧治疗组(E组),每组各8只。采用Vandman法将B-E组兔的左膝关节造模成功后,将不同浓度的臭氧注射入C、D、E组兔左膝关节腔内,剂量为1 ml,每三天一次,共注射二次。检测兔血浆中自由基的代谢变化和左膝关节软骨病理变化。结果:(1)与A组相比,B组超氧化物歧化酶(superoxide dismutase,SOD)含量显著减少(P<0.01)。与B组相比,C、D和E组SOD含量均显著增加(P<0.01)。C、D和E组组间无统计学差异。(2)与A组相比,B组一氧化氮(nitric oxide,NO)含量显著增加(P<0.01)。与B组相比,C、D和E组NO含量均显著减少(P<0.05)。C、D、E组组间无统计学差异。(3)与A组相比,B组丙二醛(malondialdehyde,MDA)含量显著增加(P<0.01)。与B组相比,C、D和E组MDA含量均显著减少(P<0.01)。D组较C组血浆中MDA含量显著减少(P<0.05)。(4)B组软骨呈典型的骨性关节炎改变,C、D组关节软骨可见不同程度修复,E组未见明显修复。结论:(1)膝关节腔内注射20μg/ml和40μg/ml臭氧可以有效的抑制关节软骨退变,对骨性关节炎具有治疗作用。(2)臭氧治疗OA的机制为抑制自由基大量释放,提高机体清除氧自由基的能力。     

PURE CULTIVATION IN VIVO OF VACCINE VIRUS FREE FROM BACTERIA

Vaccine virus freed from all associated bacteria by means of suitable disinfecting agents can be propagated in a pure state in the testicles of rabbits and bulls. The virus cultivated in this manner is not only devoid of all bacteria, but appears capable of indefinite transfer from one animal to another. Sixty passages in rabbits of a pure strain have been made within one year. Several transfers from testicle to testicle are required to bring about accurate adaptation of the virus to the testicular parenchyma, so that continued propagation in this way can be certainly secured. During the first transfers from testicle to testicle the activity of the virus may be less than the original skin specimen from which the pure strain was derived; but as the transfers proceed the activity rises until, when the adaptation is complete, the activity of the testicular equals that of the skin strain. The multiplication of the virus within the testicle is maximum on the fourth or fifth day after inoculation; the quantity of virus remains about stationary until the eighth day, when diminution begins. At the expiration of five weeks no more virus could be detected in the testicle. The vaccinal processes in the skin, cornea, and testicle of rabbits are practically identical whether the virus employed for the inoculation has been the original skin strain or the pure testicular strain; and the skin lesions produced in the calf with the two strains are also identical. In conformity with the finding mentioned in the last paragraph it has been found that human beings react to the pure testicular strain of vaccine virus in an entirely typical manner. In the case both of original vaccination and revaccination the vaccinal effects cannot be distinguished from those arising from uncomplicated skin virus. Pure strains of testicular virus are readily produced, and once secured they may be propagated in a pure state by the method described in rabbits or bulls without difficulty and with economy. The pure strains thus obtained should supply an ideal form of virus for employment in the vaccination of human beings.     

Cushing's Syndrome: AN EVALUATION OF THE CLINICAL USEFULNESS OF URINARY FREE CORTISOL AND OTHER URINARY STEROID MEASUREMENTS IN DIAGNOSIS

Urinary free cortisol excretion has been measured in a groupof 40 patients with Cushing's syndrome and in 34 patients inwhom this diagnosis was suspected on clinical grounds, but inwhom it was later disproved. Measurements were made in the basal state, during dexamethasonesuppression, and after metyrapone (when free cortisol and 11-deoxycortisolwere measured together) and the results compared with thoseof 17 oxogenic steroid measurements. In the basal state no normal or ‘suspected’ patientexcreted more than 106 µg/24 h of free cortisol whilethe lowest value seen in any patient with Cushing's syndromewas 110 µg/24 h. In 25 per cent of the patients with hyperadrenalism17 OGS excretion was within the normal range. Three patientswith ectopic ACTH produc tion all excreted more than 1000 µgof free cortisol in 24 h and in two of the three 17 OGS excretionwas greater than 100 mg/ h. During low-dose dexamethasone suppression (2 mg daily) freecortisol excretion fell to very low levels in normal and suspectedsubjects but failed to do so in patients with Cushing's syndrome,although a few patients did show suppression almost to withinthe normal range. In no patient with Cushing's syndrome did17 OGS excretion fall to less than 5 mg/24 h. However, it alsofailed to do this in 43 per cent of the ‘suspected’subjects. High-dose dexamethasone suppression (8 mg/day) failed to providea clear differentiation between patients with pituitary-dependentdisease and those with autonomous adrenal lesions or ACTH-producingtumours in terms of change in either free cortisol or 17 OGSexcretion. On metyrapone testing 96 per cent of pituitary-dependent patientsshowed a definite rise in 17 OGS excretion. We have not yetseen such a response in a patient with a non-pituitary-dependentlesion. Measurement of free F+S excretion was not ¹Present address: Department of Medicine, University Hospitalof South Manchester, Withington     

弓形虫病淋巴结炎组织中ACTH与5-HT的表达

目的探讨弓形虫病淋巴结炎组织中神经内分泌免疫网络系统共用的生物学语言:促肾上腺皮质激素(ACTH)与5-羟色胺(5-HT)表达的意义。方法应用免疫组化PictureTM二步法检测淋巴结炎组织中的弓形虫、ACTH及5-HT。将弓形虫检测结果分为阳性组与阴性组,2组ACTH与5-HT的检测结果用统计学方法对照分析。结果50例淋巴结炎组织中有16例弓形虫阳性。ACTH与5-HT阳性标志物在2组淋巴结炎组织中分布大致相似,主要位于副皮质区的T淋巴细胞、淋巴滤泡生发中心细胞及巨噬细胞等部位,但表达强度有显著性差异(P<0.05)。结论弓形虫可引起神经内分泌免疫网络中的ACTH与5-HT表达强度增强,可能与弓形虫病淋巴结炎的发生与病情发展有一定的关系。     

异博定和氯化钙对电针镇痛效果及小鼠脑细胞游离钙镁浓度的影响

目的 :进一步探讨针刺镇痛机理。方法 :用离子探针Fura -2 -AM和Furaptra -AM配合高敏度AR -CM -MIC阳离子测定系统分别测定了异博定和氯化钙对电针的镇痛效果及小鼠下丘脑 (HT)和导水管周围灰质区 (PAG)细胞内游离钙离子浓度 ( [Ca2 +]i )及游离镁离子浓度 ( [Mg2 +]i )的变化。结果 :电针小鼠拟“人中”、“承浆”穴 ,上述两脑区 [Ca2 +]i均明显降低 ,而 [Mg2 +]i则略有升高 ,[Ca2 +]i/[Mg2 +]i比值明显降低 ;小鼠脑室内注射少量CaCl2 及腹腔注射钙通道阻断剂异博定(verapamil)均可抑制电针的镇痛效应。结论 :电针镇痛效果可能与细胞内的游离钙镁离子浓度比值有关。     

晶体盐溶液保存血小板的初步研究

对2种不同纽成成分的晶体盐液分别进行过滤除菌或高压灭菌处理,并用自体血浆作对照,分别保存同一份血小板样品。晶体盐液Medium_(13)(MD_(13))含有枸橼酸盐、磷酸盐和葡萄糖等成分,Medilum t(MD_t)除上述成分外,还含有茶碱(1,3-二甲基黄嘌呤),血小板在不同类型的介质中保存7天后,血小板的功能及形态变化各组间无显著差别,但pH与第一天相比均显著下降;MDt溶液保存血小板7天后,其乳酸含量明显低于同期在血浆中保存者,而pH基本维持在同一水平。根据试验结果,我们认为MD_(13)和MD_t2种晶体盐溶液能代替自体血浆保存血小板。     

LOCALIZATION OF FREE AND BOUND SECRETORY COMPONENT IN HUMAN INTESTINAL EPITHELIAL CELLS : A MODEL FOR THE ASSEMBLY OF SECRETORY IgA

Antibody reagents were made specific for each of the two forms of human SC, FSC and BSC, which is an integral part of the sIgA molecule. With the fluorescent antibody method the cytological and histological localization of FSC, BSC, and α-chains has been studied in various human mucous membranes. SC was present in columnar epithelial cells of the intestines and in the cells of serous acini of bronchial and salivary glands. In contrast, SC was not found in intestinal goblet cells or cells of mucous acini of bronchial and salivary glands. In the columnar epithelial cells of the small and large bowel, FSC was present most prominently in the Golgi zone, and much less prominently in the apical cytoplasm. On the other hand, BSC and α-chains were located only in the apical cytoplasm in an overlapping manner. The results favor a model in which sIgA is assembled inside epithelial cells from SC, which was synthesized in the same cell, and IgA, which entered the epithelial cell after synthesis in and secretion by a plasma cell.