RELATIONSHIP OF VIRUS DOSE TO INCUBATION TIME OF CLINICAL HEPATITIS AND TIME OF APPEARANCE OF HEPATITIS - ASSOCIATED ANTIGEN

RELATIONSHIP OF VIRUS DOSE TO INCUBATION TIME OF CLINICAL HEPATITIS AND TIME OF APPEARANCE OF HEPATITIS - ASSOCIATED ANTIGEN
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DOI:
10.1097/00000441-197201000-00005
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发表时间:
1972-01-01
影响因子:
3.1
通讯作者:
MURRAY, R
MURRAY, R
中科院分区:
医学4区
文献类型:
--
作者:
BARKER, LF;MURRAY, R

文献摘要

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用微量补体结合试验检测了1951-1954年间进行的血清肝炎向志愿者传播实验的冰冻黄原性血浆池标本和冰冻血清标本中的乙肝抗原。37名受试者皮下注射1毫升未稀释的血浆池,其中22人在45~92天后出现临床肝炎,平均潜伏期为77天。37例受者中有25例在接种后42~82天检测到该抗原,平均62天。2例接种10-3稀释度血浆后临床肝炎潜伏期分别为92天和130天,1例在接种10-3稀释度后119天出现临床肝炎。13名血浆稀释度在10-3~10-7之间的受试者在较长的潜伏期后获得了血清中的抗原,其中只有3名受试者发生了临床性肝炎。经中位数试验比较,接种未稀释血浆后出现乙肝抗原的时间明显短于接种L后(H~(-7)稀释度的血浆池。同时研究了不同处理对血浆池的影响。紫外线照射血浆池后,临床疾病潜伏期(82~134天,平均100天)和血清中抗原出现的时间(61~99天,平均79天)均明显长于注射未经处理的致黄血浆后的相应潜伏期。一些受试者在接种以其他方式处理的血浆后出现临床肝炎和抗原。血浆在60°C加热2小时和4小时后的潜伏期是分散的,与未经处理的血浆的孵化时间相比仅略有增加。接种在22~25℃保存3个月的血浆或经β-丙内酯治疗后出现临床肝炎或血清抗原或两者兼有的潜伏期有延长的趋势,但病例数太少,不能进行统计分析。5名受试者皮下接种从致黄血浆池中分离锌制备的4毫升γ-球蛋白,均可诱发抗原-B阳性肝炎。必须强调的是,这批锌沉淀法制备的γ-球蛋白与目前用乙醇分级法制备的γ-球蛋白(免疫血清球蛋白)不可同日而语。的确,通过乙醇分离黄原性血浆池制备的γ球蛋白不会传播肝炎。]给予锌沉淀γ球蛋白的受试者的孵育时间长于原未稀释血浆池的受者,接种稳定的血浆蛋白溶液和静脉注射100ml白蛋白后的孵育时间也长于原血浆池接种后的孵育时间。该白蛋白制剂在60℃加热10小时后,15例100毫升静脉接种者未发现临床肝炎或乙肝抗原。2名确诊肝炎携带者接种1毫升血清后,与其中一名携带者的血清潜伏期较短:39~60天(平均38天),与第二携带者的血清潜伏期略长。最后,一批含人凝血酶诱发6例临床肝炎,平均潜伏期88天。4例…患者中检出乙肝病毒抗原
Samples from a frozen icterogenic plasma pool and frozen serum specimens from experiments on the transmission of serum hepatitis to volunteers conducted in 1951 to 1954 were tested for hepatitis B antigen by the microtitre complement-fixation test.Of the 37 subjects who received 1 ml sub-cutaneously of the undiluted plasma pool, 22 developed clinical hepatitis 45 to 92 days later, with an average incubation period of 77 days. The antigen was detected in 25 of the 37 recipients 42 to 82 days after inoculation, with a mean of 62 days.The incubation periods of clinical hepatitis in 2 cases which followed inoculation of a 10-3dilution of plasma were 92 and 130 days, whereas I individual developed clinical hepatitis 119 days after inoculation of 10-3dilution. 13 recipients of dilutions of plasma from 10-3to 10-7acquired the antigen in their serum after longer incubation periods; and only 3 of these subjects developed clinical hepatitis. Comparison by the median test showed the time of appearance of hepatitis B antigen after inoculation of the undiluted plasma to be significantly shorter than after inoculation with l(H to 10-7dilutions of the plasma pool.The effect of various treatments of the plasma pool was also studied. After ultraviolet irradiation of the plasma pool, both the incubation period of the clinical illness (82 to 134 days, average 100 days) and the time of appearance of the antigen in the serum (61 to 99 days, average 79 days) were significantly longer than the respective incubation times following the injection of the untreated icterogenic plasma. Several subjects developed clinical hepatitis and antigen after the inoculation of plasma treated in other ways. The incubation periods after the plasma had been heated for 2 and 4 hours at 60°C were scattered and only slightly increased compared with the incubation times following untreated plasma. There was a tendency for the incubation period to be increased when clinical hepatitis or serum antigen, or both, developed after inoculation of plasma which had been stored for 3 months at 22-25 °C or had been treated with β-propiolactone, but the number of cases was too small for statistical analysis.Antigen-B-positive hepatitis was induced in each of 5 subjects inoculated subcutaneously with 4 ml of γ-globulin which had been prepared from the icterogenic plasma pool byzinc fractionation. [It must be stressed that this batch of γ-globulin prepared by zinc precipitation isnotcomparable with current γ-globulin (immune serum globulin) which is prepared by ethanol fractionation. Indeed, γ-globulin prepared by ethanol fractionation of the icterogenic plasma pool did not transmit hepatitis.] The incubation times in the subjects givenzinc precipitatedγ-globulin were longer than in the recipients of the original undiluted plasma pool.The incubation times following the inoculation of stable plasma protein solution and of 100 ml of albumin given intravenously were also longer than the incubation times after inoculation of the original plasma pool. After this preparation of albumin had been heated for 10 hours at 60°C, no clinical hepatitis or hepatitis B antigen was noted in 15 recipients of 100 ml intravenous inoculations.The inoculation of 1 ml of serum from 2 proven hepatitis carriers induced clinical hepatitis accompanied by hepatitis B antigen after relatively short incubation periods: 39 to 60 days (average 38 days) with the serum of one of the carriers, and slightly longer incubation periods with the serum of the second carrier.Finally, a batch of human thrombin containing hepatitis B antigen induced clinical hepatitis in 6 subjects, with an average incubation period of 88 days. Hepatitis B antigen was detected in 4 of …