原发性胆汁性肝硬化患者自身抗体检测及其临床意义

目的 探讨血清自身抗体对原发性胆汁性肝硬化(PBC)的诊断及其临床意义.方法 对PBC患者采用间接免疫荧光、免疫印迹法检测抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA),并对AMAM2亚型及其抗可溶性肝抗原/肝胰抗原(SLA/Le)、抗肝肾微粒体Ⅰ型(LKM-1)和抗肝特异性胞浆Ⅰ型抗体(LC-1)等肝脏疾病相关的自身抗体进行检测.结果 PBC患者自身抗体以AMA和AMAM2亚型为主.其阳性率分别为96.5%和93.1%.患者的抗体滴度均大于1:100,其中有8例出现ANA和SMA,1例出现AMA和SLA/LP同时阳性,表现与Ⅰ型和Ⅲ型自身免疫性肝炎重叠,另有19例AMAM2阳性患者进行肝穿病理检查时,12例(63.7%)患者病理提示符合PBC诊断.结论 自身抗体对PBC有诊断意义,注重自身抗体的检测对明确自身免疫性肝病有重要的临床意义.     

自身免疫性肝病临床及免疫学特征

目的 分析自身免疫性肝病的临床特征和免疫学特点,以提高对该类疾病的认识和诊断水平.方法 对164例自身免疫性肝病患者的临床症状、体征及免疫学检查资料进行回顾性分析.结果 原发性硬化性胆管炎(PSC)多发于青年男性,自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(AIH-PBC)多发于中年女性;临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84%、78%、90%和67%,皮肤瘙痒的发生率分别为43%、56%、81%和60%.但AIH、PBC和PBC-AIH患者之间的年龄、性别、黄疸、皮肤瘙痒等症状无显著性差异(P均＞0.05).AIH首诊正确诊断率为8%(6/77),PSC为9%(1/11),PBC为13%(6/46).从发病到确诊PBC平均为38月,AIH为46月,PSC为31月,PBC-AIH重叠综合征确诊最难,平均需51月,常误诊为可能的AIH或单纯PBC.AIH、PBC、PSC和PBC-AIH肝外自身免疫性疾病的发生率分别为47%、11%、27%和24%,各自身免疫性肝病患者均有较高的自身抗体发生率.结论 自身免疫性肝病在临床上并不少见,患者常伴发肝外自身免疫性疾病及较高的自身抗体发生率;诊断需综合临床、生化、自身抗体和病理组织学等指标.     

早期原发性胆汁性肝硬化的诊断(附20例病例分析)

目的 分析20例早期原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者的临床、生化及病理特征,以早期诊断、早期治疗.方法 20例早期PBC患者的一般资料、病程、临床表现、血清化学指标、免疫学及病理学改变等进行分析.结果 本组患者中女16例,男4例,确诊时年龄25～74岁,平均48.2岁.确诊时间为0.5～24月.早期PBC临床表现缺乏特异性,常见表现有纳差(40%)、乏力(35%)、尿黄(35%)、黄疸(30%),9例无症状仅发现ALP、GGT升高(45%).所有病例中AMA-M2阳性13例(65%)、gp210阳性4例(20%)、SP100阳性3例(15%).肝脏组织病理学检查为Ⅰ～Ⅱ期表现.结论 早期PBC临床表现不典型,可无症状或有乏力、纳差等非特异性表现.对ALP、GGT升高或(和)AMA-M2、gp210、SP100阳性患者要考虑PBC可能,对中老年人群.特别足女性筛查肝功能和自身免疫性肝病抗体,完善肝脏组织学检查可帮助早期诊断PBC.     

原发性胆汁性肝硬化血清免疫学检测的临床意义

目的 分析PBC患者的自身抗体和免疫功能,探讨其对PBC的诊断价值.方法 连续纳入确诊的PBC患者50例,以免疫印迹法检测肝特异性自身抗体,以间接免疫荧光法检测肝非特异性自身抗体,以免疫散射比浊法检测免疫球蛋白和补体,30例行肝穿刺活检组织病理学检查.结果 本组PBC患者女性多于男性(419),年龄20～83岁,平均55.9岁±13.2岁.肝特异性自身抗体中AMA-M2阳性最为多见(68%),其次为GP210抗体(22%)、核点蛋白SP100抗体(14%)、肝肾微粒体1型(LKM-1)抗体(10%)、和肝细胞溶质抗原Ⅰ型(LC-1)抗体(2%),肝非特异性自身抗体以抗核抗体(ANA)检出率最高(61%).结论 自身抗体,尤其是血清AMA-M2阳性是诊断PBC的重要依据之一,但多种蛋白在PBC病程中均有表达,且临床上有相当比例的AMA-M2阴性PBC患者.其他肝特异性自身抗体如SP100抗体、GP210抗体等以及临床特点和肝穿刺活检对AMA-M2阴性PBC的诊断有重要价值.     

自身免疫性胆管炎

正常胆汁的排泌不畅造成胆汁瘀积 ,最终导致肝脏组织形态学改变形成肝硬化。原发性胆汁性肝硬化 (PBC)为成人由于肝内胆管异常造成慢性瘀胆的常见疾病。一般认为 ,PBC是一种自身免疫介导的非化脓性破坏性肝内胆管炎 ,95 %的PBC患者抗线粒体抗体 (AMA )阳性 ,其对PBC的诊断尤其是AMA M 2特异性达 98%。近来发现有 10 %PBC患者AMA阴性 (间接免疫荧光法 ) ,其瘀胆的生化指标和肝穿病理与AMA阳性的PBC患者相似 ,但抗核抗体或抗平滑肌抗体阳性率高 ,被称为自身免疫性胆管炎 (AIC) [1 ] 。该病是否为独立的疾疾或是PBC或自身免疫性…     

20例原发性胆汁性肝硬化自身抗体和免疫功能分析

背景:一般认为血清抗线粒体抗体M2亚型(AMA-M2)阳性是诊断原发性胆汁性肝硬化(PBC)的必备标准,但仍存在一定比例的AMA-M2阴性PBC患者。因此,了解PBC患者的自身抗体谱和免疫功能有助于PBC的诊断。目的:分析PBC患者的自身抗体和免疫功能,探讨其对PBC的诊断价值。方法:连续纳入确诊的PBC患者20例,以免疫印迹法检测肝特异性自身抗体,以间接免疫荧光法检测肝非特异性自身抗体,以免疫散射比浊法检测免疫球蛋白和补体;13例患者行肝穿刺活检组织病理学检查。结果:本组PBC患者女性多于男性(17:3),年龄39～75岁,平均57.2岁±2.1岁。肝特异性自身抗体中AMA-M2阳性最为多见(40%),其次为核点蛋白SP100抗体(15%)、肝肾微粒体1型(LKM-1)抗体(15%)、GP210抗体(10%)和肝细胞溶质抗原Ⅰ型(LC-1)抗体(10%);肝非特异性自身抗体以抗核抗体(ANA)检出率最高(70%);IgA、IgM和IgG升高者均占50%。结论:自身抗体,尤其是血清AMA-M2阳性是诊断PBC的重要依据之一,但多种蛋白在PBC病程中均有表达,且临床上有相当比例的AMA-M2阴性PBC患者。其他肝特异性自身抗体,如SP100抗体、GP210抗体等以及临床特点和肝穿刺活检对AMA-M2阴性PBC的诊断有重要价值。     

抗线粒体抗体阴性原发性胆汁性肝硬化的临床特征

目的　原发性胆汁性肝硬化 (PBC )的最重要特征为血清抗线粒体抗体 (AMA )阳性 ,但少数PBC病例AMA阴性。本文分析AMA阴性PBC患者的临床、生化和免疫学特性。方法　对 1991年 1月～ 2 0 0 2年 7月期间临床 /病理诊断PBC的 70例患者进行回顾性研究 ,分析比较AMA阴性和AMA阳性患者的一般资料、病程、临床表现、生物化学、免疫学及病理学等特征。结果　确诊PBC时 ,11例患者血清AMA/AMA M2 阴性 ,AMA阴性患者的血清免疫球蛋白M显著低于AMA阳性患者 ,分别为 (2 85 1± 14 18)mg/L和 (63 61± 492 8)mg/L ,P =0 .0 3 3 ,血清抗核抗体和 (或 )抗平滑肌抗体阳性率高于AMA阳性患者 (分别为 81.8%和 40 .7% ,P =0 .0 3 1) ,在年龄、性别比例、临床表现、肝功能试验、组织学表现和病理分期等各方面和AMA阳性患者无显著性差异。结论　AMA阴性PBC患者除血清免疫球蛋白M较低及抗核抗体和 (或 )抗平滑肌抗体阳性率较高外 ,其他临床特征和AMA阳性者相似     

18例无症状期原发性胆汁性肝硬化诊断特点分析

背景：原发性胆汁性肝硬化（PBC）进展缓慢,从无症状至出现症状,时间可长达数年。无症状期PBC临床表现缺乏特异性,诊断较为困难。目的：总结无症状期PBC的诊断特点。方法：纳入18例无症状期PBC患者,检测并分析其一般情况、临床、生化、病毒学、免疫学、影像学和组织学表现。结果：18例无症状期PBC患者中男2例,女16例,确诊时平均年龄47.8岁。无临床和生化异常,仅抗线粒体抗体M2亚型（AMA-M2）阳性者9例;因肝功能异常,主要是碱性磷酸酶（ALP）、γ-谷氨酰转肽酶（GGT）升高而就诊者9例,确诊时间平均8.9个月。11例（61.1%）患者AMA-M2阳性,3例gp210抗体阳性,2例SP100抗体阳性。所有患者肝穿刺病理学检查均为Ι、Ⅱ期PBC表现。结论：无症状期PBC女性多见,可仅表现为AMA-M2和（或）gp210、SP100抗体阳性,以及ALP/GGT升高。对中老年人群特别是女性,筛查肝功能和自身免疫性肝病抗体以及完善肝脏组织学检查有助于早期诊断PBC。     

自身免疫性肝病109例的临床与病理特征分析

目的 分析比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)及AIH重叠综合征的临床特点、生化特征和组织学变化,以提高对自身免疫性肝病(AILD)的认识.方法 收集2004年1月-2008年6月肝穿刺病理学检查确诊的AILD患者共109例,其中AIH 27例、PBC 67例、PSC 4例、AIH-PSC重叠综合征1例和AIH-PBC重叠综合征10例,对患者的临床及实验室检查资料进行回顾性分析.结果 AILD患者多发于中年女性(73.3%,80/109),常见症状为黄疸、乏力、纳差和皮肤瘙痒.AIH患者的发病年龄高峰在50岁左右,肝功能检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常值,62.9%的患者(17/27)抗核抗体(ANA)阳性.肝组织病理变化以界面性肝炎为主(77.7%),在重度患者则出现重度界面件肝炎、桥样坏死等.PBC患者主要表现为碱性磷酸酶、γ-谷氨酰转肽酶和胆红素明显升高,伴免疫球蛋白M升高,74.6%的患者(50/67)线粒体抗体(AMA)和(或)AMA-M2亚型阳性.所有PBC患者行肝脏病理学检查,早期(Ⅰ、Ⅱ)占28.3%,晚期(Ⅲ、Ⅳ)占71.7%,肝组织病理变化以小胆管减少甚至消失为主(62.6 0A).AIH-PBC重叠综合征患者的临床表现和肝组织病理学具有AlH和PBC的双重特征,其中有3例患者同时检测到ANA和AMA/AMA-M2阳性.结论 AILD在中国人中并非少见,其诊断需综合临床表现、生化、免疫指标和组织学变化.     

35例自身免疫性肝病的临床特点与分析

目的分析比较三种自身免疫性肝病(ALD)的临床表现、血清学和病理学特点及诊断意义.方法回顾性总结昆明医学院第二附属医院2003～2005年35例自身免疫性肝病患者的临床资料.结果①临床表现:ALD以中年女性多见,自身免疫性肝炎(AIH)和原发性硬化性胆管炎(PSC)在年龄上有显著差异,PSC的发热症状较AIH和原发性胆汁性肝硬化(PBC)明显,常伴有胆系感染;②实验室检查:AIH表现为球蛋白显著升高,同时AST、ALT及ALP、GGT升高显著,PSC的TB和DB水平最高,IgG在AIH、PSC中的浓度与PBC比较有显著性差异,明显增高.同时IgA在PSC中浓度与AIH、PBC比较有显著性差异,其浓度明显高于其它两种ALD,AIH患者ANA阳性检出率为75%,可能存在AIH-PSC重叠综合症,其发生率约占17.6%;③影像学检查:PSC患者100%有肝内、外胆管的僵硬、狭窄、变细或局部扩张;④病理学:共有6例行肝穿刺病理活检,病理结果提出明确诊断者2例(33.3%).结论ALD临床表现复杂多样但各有特点,血清免疫学及抗体检测有助于AIH与PBC的诊断和鉴别诊断,ERCP或MRCP有助于PSC的确诊,病理学检查的诊断价值有一定的局限性.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.