Imbalance in recruitment of IgG (Gm) allotype-producing B-cell subsets from blood to brain in multiple sclerosis

In Gm3/Gm3 homozygous multiple sclerosis (MS) patients, in vitro production of the G1m(3) allotype of IgG1 induced by the T-independent polyclonal B-cell activator Salmonella paratyphi B (SPB) was lower than that of normal individuals of the same Gm phenotype. In contrast, lymphocytes from Gm1/Gm3 heterozygous MS patients responded to the same stimulus with a significantly increased G1m(3) allotype synthesis not observed in normal individuals of the same phenotype. The high level of intrathecal IgG1 production observed in MS patients might be achieved by a selection at the blood-brain barrier of some peripheral T-independent B-cell clones which in Gm3/Gm3 homozygous would bear the G1m(3) allotype, hence a peripheral depletion of this subset, whereas in Gm1/Gm3 heterozygous a preferential admission of the G1m(1)-producing B-cells would lead to a preferential synthesis of this allotype in the central nervous system and to a relative increase of G1m(3) production by the remaining peripheral B cells.     

Serum Gc system in liver cirrhosis and hepatoma

Summary Serum Gc polymorphism was studied in 85 patients with liver cirrhosis, in 65 with cirrhosis plus hepatoma, and in 40 with hepatoma without cirrhosis. Six hundred unrelated healthy Greeks served as controls. The Gc 1-1 phenotype was found more frequently in patients who had cirrhosis with or without hepatoma but the incidence of the Gc¹ gene was significantly higher in patients with cryptogenic-HBsAg negative cirrhosis. On the other hand, the Gc 2-2 phenotype was found about three times more frequently in patients who had hepatoma without cirrhosis, and the incidence of the Gc² gene was significantly higher in the same group than in the controls. Consequently, it could be surmised that the Gc¹ and the Gc² genes predispose, under the influence of various factors, the development of cryptogenic cirrhosis and hepatoma without cirrhosis, respectively.     

Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography

In order to clarify the underlying mechanism of malignant transformation from cirrhosis to hepatoma the cell kinetics of hepatocytes were studied in these two conditions. The content and synthesis of DNA in hepatocyte nuclei were investigated, by means of Feulgen-microspectrophotometry and tritiated thymidine radioautography, in cirrhotic and noncancerous parts of hepatoma with concomitant cirrhosis. The distribution of ploidy patterns was widely spread, from hypodiploid to hyperpolyploid, in the noncancerous parts of a cirrhotic liver containing hepatoma. In normal liver, each paired nuclear DNA content of a binucleate cell recorded almost the same amount, whereas in the noncancerous as well as in hepatoma cells much difference of DNA content was observed between the paired nuclei of the binucleate cells. The ploidy pattern of hepatocytes in patients with liver cirrhosis, who had developed hepatoma during follow-up periods of several months to several years, appeared to resemble that in noncancerous parts of hepatoma cases. On the other hand, the incorporation of tritiated thymidine into hepatocytes was found to be markedly increased in noncancerous parts as well as in cirrhotic liver developing hepatoma during follow-up periods. These results suggest the possibility that the hepatocytes in noncancerous parts of hepatoma have deranged cell-kinetics which might be a driving factor for the development of malignancy.     

Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography

Summary In order to clarify the underlying mechanism of malignant transformation from cirrhosis to hepatoma the cell kinetics of hepatocytes were studied in these two conditions. The content and synthesis of DNA in hepatocyte nuclei were investigated, by means of Feulgen-microspectrophotometry and tritiated thymidine radioautography, in cirrhotic and noncancerous parts of hepatoma with concomitant cirrhosis. The distribution of ploidy patterns was widely spread, from hypodiploid to hyperpolyploid, in the noncancerous parts of a cirrhotic liver containing hepatoma. In normal liver, each paired nuclear DNA content of a binucleate cell recorded almost the same amount, whereas in the noncancerous as well as in hepatoma cells much difference of DNA content was observed between the paired nuclei of the binucleate cells. The ploidy pattern of hepatocytes in patients with liver cirrhosis, who had developed hepatoma during follow-up periods of several months to several years, appeared to resemble that in noncancerous parts of hepatoma cases. On the other hand, the incorporation of tritiated thymidine into hepatocytes was found to be markedly increased in noncancerous parts as well as in cirrhotic liver developing hepatoma during follow-up periods. These results suggest the possibility that the hepatocytes in noncancerous parts of hepatoma have deranged cell-kinetics which might be a driving factor for the development of malignancy.     

Genotype Distribution of Vitamin D Receptor Polymorphisms among Indonesian Patients with Chronic Hepatitis B

Background:Chronic hepatitis B is a necro-inflammatory of the liver parenchyma caused by hepatitis B virus (HBV) infection leading to liver cirrhosis and hepatocellular carcinoma (HCC). Genetic variants including single nucleotide polymorphisms (SNPs) within genes regulating immune response may contribute to the progression of chronic hepatitis B (CHB) infection. This study aimed to examine the genotype distribution of vitamin D receptor (VDR) polymorphism among patients with CHB infection and to study its association with the development of cirrhosis and hepatoma.Methods:This cross-sectional study analysed 75 CHB patients, consisting of 36 CHB patients without cirrhosis, 25 CHB patients with cirrhosis, and 14 CHB patients with hepatoma. VDR polymorphism was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) method.Results:Alanine aminotransferase (ALT) and alpha fetoprotein (AFP) levels did not show any significant differences between study groups, but albumin levels in CHB patients with cirrhosis and hepatoma were significantly lower than CHB patients without cirrhosis (p< 0.05). In contrast, the bilirubin levels in CHB patients with cirrhosis was higher than in CHB patients’ cirrhosis. The most common genotypes of VDR polymorphisms were Ff (57.3%), TT (72%), aa (48%) and bb (74.7%) for Fok1, Taq1, Apa1 and Bsm1 respectively. There was no significant different in the genotype distribution of VDR polymorphism between CHB patients without cirrhosis and CHB with cirrhosis or hepatoma. Conclusion:This study suggest that VDR gene polymorphism may not contribute to the progression of CHB infection.Key Words: Cirrhosis, Hepatitis B, Hepatoma, Polymorphism, Vitamin D Receptor     

慢性牙周炎与原发性肝硬化的相关性分析

目的:探究慢性牙周炎与原发性肝硬化之间的相关性。方法:选择2017年1月至2019年1月于我院接受治疗的60例原发性肝硬化患者为研究组,选择同期于我院接受体格检查的100例健康个体为对照组,对两组患者分别实施牙周检查,对比两组患者牙周炎发生率,分析吸烟、饮酒对牙周炎发生率影响,按照Child-改良分级法对肝硬化患者进行评分并分级,对比各级原发性肝硬化患者慢性牙周亚发生率,并就慢性牙周炎与肝硬化相关性进行分析。结果:(1)对照组慢性牙周炎发生率显著低于研究组慢性牙周炎发病率(44.00%vs. 71.67%,P0.05);(2)研究组和对照组中吸烟者的慢性牙周炎患病率显著高于不吸烟者(P0.05),研究组中吸烟者发生慢性牙周炎患病率高于对照组,对比无统计学意义(P0.05);研究组和对照组饮酒者的慢性牙周炎患病率显著高于不饮酒者(P0.05),研究组中饮酒者发生慢性牙周炎患病率显著高于对照组(P0.05);(3)随着原发性肝硬化患者评分的升高,患者牙周炎患病率也随之上升,牙周附着丧失程度也出现加剧(P0.05)。结论:原发性肝硬化患者慢性牙周炎患病率高于健康个体,随着肝硬化患者病情的加剧,患者慢性牙周炎发生率也随之上升;另外,吸烟及饮酒会增加健康个体慢性牙周炎患病率。     

Cyclooxygenase-2 single-nucleotide polymorphisms and hepatocellular carcinoma in Egypt

Hepatocellular carcinoma (HCC) is a worldwide neoplasm for which early diagnosis is difficult and the prognosis is usually poor. Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with hepatocarcinogenesis. Although several COX-2 inhibitors have been used in hepatoma therapy, the genetic background between COX-2 and HCC remains largely unknown. In this study, the association of genotypic polymorphisms in COX-2 with HCC was investigated. 25 healthy individuals served as control (group I), group II: 50 HCV infection patients without any complications, group III: 50 HCV infected patients complicated with cirrhosis and group IV: 75 HCV infected patients complicated with (45 localized and 30 metastatic) HCC from Zagazig University Hospital in Egypt were genotyped by a PCR–RFLP method. The results showed that, no differences in distribution between the HCC and other groups were found. We found ?1195A allele carriers had a higher risk of HCC with HCV infection. As regard the obtained results of serum AFU, a significant increase was detected in HCC as compared with cirrhosis, hepatitis and healthy control groups (p < 0.001). Concerning the obtained results of serum AFP, when HCC group was compared with cirrhosis, hepatitis and healthy controls, a significant increase was observed (p < 0.001). In conclusion: identification of SNP in COX-2 gene promoter and evaluation of serum AFU and AFP give a red light in early detection of HCC which may be reduce its fatal incidence.     

中国人免疫球蛋白同种异型的研究:中华民族起源的一个假说

调查了我国24个民族、74个群体的免疫球蛋白同种异型Gm、Km分布。测定了9560例个体的Gm(1,2,3,5,21)因子和9611例个体的Km(1)因子。根据Gm单体型频率计算了遗传距离并绘制了系统树。结果支持作者早前提出的有关中华民族起源于古代两个不同群体的假说。这两个群体大致以北纬30度为界,分别居栖在黄河和长江流域。本文数据和其他主要人种的Gm分布资料相比较,作者认为在人类进化中,尼格鲁人种首先和高加索-蒙古人种分离;然后高加索人种和蒙古人种分离。不同人种间的差异,大于同一人种内不同群体间的差异。蒙古人种明显地被分为南、北两大类型,分别以具有高频率的Gm~(1;21)和Gm~(1,3;5)单体型作为种族的标记。与高加索人种关联的Gm~(3;5)单体型存在于中国西北地区的少数民族中,提示混有高加索人种血缘。很可能来源于中亚地区的高加索人,通过“丝绸之路”进入中国。Km因子在所调查的74个群体中呈随机分布。     

肝硬化患者术后感染的危险因素及干预措施

目的:感染是肝硬化患者肝移植术后常见的并发症之一,影响患者的治疗效果和生存质量。本文针对肝硬化患者术后感染的危险因素进行分析,探讨有效的干预措施以提高临床疗效,为肝硬化术后并发症的预防提供可借鉴的方法。方法:对2008年10月-2013年9月在我院接受手术治疗的120例肝硬化患者的临床资料进行回顾性分析。根据术后并发症的发生情况选择其中60例发生感染的患者作为感染组,另外60例未发生感染的患者作为对照组。观察两组患者的年龄、肝硬化分期及用药情况等,对比不同的干预措施产生的临床效果。结果:感染组患者的平均年龄、肝功能障碍、抗生素使用量及术前合并感染的比率均显著高于正常对照组,差异具有统计学意义(P0.05)。两组患者进行针对性的护理干预均获得良好的治疗效果,未发生死亡病例。结论:患者的年龄、肝功能分级、用药及合并症等均为肝硬化术后感染的危险因素,临床中应实施针对性的干预措施以提高疗效。     

Th17及相关细胞因子与酒精性肝硬化患者肝脏硬度值、肝功能及脂联素水平的相关性分析

摘要 目的：探讨Th17及相关细胞因子与酒精性肝硬化患者肝脏硬度值（LSM）、肝功能及脂联素（APN）水平的相关性分析。方法：以2018年1月~2020年1月本院收治的酒精性肝硬化患者72例作为酒精性肝硬化组,同期在本院进行体检的健康志愿者100例作为健康对照组。对比两组研究对象Th17、白介素-17（IL-17）、LSM、肝功能指标、APN水平的差异,采用Pearson检验评估酒精性肝硬化患者Th17及IL-17与病情相关指标的相关性。结果：酒精性肝硬化组患者的Th17细胞分布比例、IL-17水平、LSM均高于健康对照组（P<0.05）。外周血中谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（STB）的水平高于健康对照组,白蛋白（ALB）的水平低于健康对照组,血清中APN的水平低于健康对照组（P<0.05）。相关性分析发现,酒精性肝硬化患者Th17细胞分布比例及IL-17水平与LSM、ALT、AST、STB的水平呈正相关,与ALB、APN的水平呈负相关（P<0.05）。结论：酒精性肝硬化患者Th17及其细胞因子IL-17表达水平异常增高,可能在反映病情相关指标异常变化程度方面具有积极作用。     

Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency.

The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of alpha-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and alpha-1-antitrypsin deficiency.     

Serum Selenium Levels in Korean Hepatoma Patients

The aim of this study was to determine serum selenium (Se) levels during the development of liver disease as well as the possible Se supplementation benefits in liver disease patients. Serum was collected from 187 patients with liver diseases and 120 normal healthy people living in Seoul. The samples were collected at the Kangnam St. Mary's Hospital College of Medicines, The Catholic University of Korea, in accordance with procedures approved by the Institutional Review Board of the Catholic University of Korea. Serum Se levels were quantified by inductively coupled plasma mass spectrometry and were compared between healthy and liver diseases patients. Se levels were 92.65?±?32.50?μg/l in hepatitis infection, 92.33?±?30.66?μg/l in hepatitis B virus infection and 96.41?±?51.50?μg/l in hepatitis C virus infection, 96.42?±?32.80?μg/l in cirrhosis, and 67.47?±?14.30?μg/l in hepatoma patients. Findings were significantly lower in hepatitis and hepatoma as compared with the healthy participants (P?相似文献   

Can we reduce oxidative stress with liver transplantation?

BackgroundThe aim of this study was to determine the levels of lipid peroxidation (MDA) and antioxidants such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the blood serum of patients with cirrhosis and liver transplantation.MethodsIn this study, serum malondialdehyde acid (MDA) levels, superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) activities were measured spectrophotometrically and compared to the results of the healthy control group.ResultsSOD, CAT and GSH activities were significantly decreased in the patient groups compared to the healthy control group (p<0.05). MDA levels were significantly higher in the patient group compared to the healthy control group (p <0.05).ConclusionsIn conclusion, this study demonstrated that oxidative stress may play an important role in the development of liver cirrhosis and in liver transplantation. This study is the first one to show how MDA, SOD, CAT and GSH levels change in liver cirrhosis and liver transplantation, while further studies are essential to investigate antioxidant enzymes and oxidative stress status in patients with cirrhosis and liver transplantation.     

Clinical utility of red cell distribution width in alcoholic and non-alcoholic liver cirrhosis

Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value < 130 g/L in men and < 120 g/L in women, which were hospitalized in our Division in a period between 2006 and 2008. Patients were divided in two groups; in first were patients with alcoholic liver cirrhosis, and in second with non-alcoholic cirrhosis. Severity of disease was determined according to Child-Pugh score. Red blood cells distribution width Normal reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.     

微生态制剂治疗肝硬化肠功能紊乱患者的临床观察

目的探讨微生态制剂治疗肝硬化肠功能紊乱患者的疗效。方法选择80例肝硬化肠功能紊乱患者,随机分成治疗组和对照组。治疗组:常规保肝治疗加金双歧(4粒/次,2次/d);对照组:常规保肝治疗。疗程均为4周。结果治疗组和对照组相比,腹胀、腹泻、腹部不适症状明显改善,血氨水平降低,血浆内毒素水平下降,2组相比差异有显著性(P<0.05)。结论微生态制剂对于改善肝硬化患者临床症状有肯定的价值,并可降低血氨及血浆内毒素水平,有利于肝功能的改善。     

IgG heavy-chain (Gm) allotypes in familial polyposis coli.

Serum samples from 40 Danish patients with familial polyposis coli and 105 normal blood donors were typed for eight Gm and one Km markers. The distribution of all Gm phenotypes as a group was significantly different in the patient population as compared to the controls. Examination of individual Gm phenotypes showed an increased frequency of Gm3;5,13 in the patients.     

Gm and Km allotypes in 74 Chinese populations: a hypothesis of the origin of the Chinese nation

Summary This paper reports the distribution of immunoglobulin Gm and Km allotypes in 74 Chinese geographical populations. These populations are derived from 24 nationalities comprising 96.6% of the total population of China. A total of 9,560 individuals were phenotyped for Gm(1,2,3,5,21) factors, and 9,611 were phenotyped for Km(1). Phylogenetic trees were constructed on the basis of Gm haplotype frequencies and genetic distances. The results of cluster analysis show the heterogeneity of the Chinese nation, and confirm the hypothesis that the modern Chinese nation originated from two distinct populations, one population originating in the Yellow River valley and the other originating in the Yangtze River valley during early neolithic times (3,000–7,000 years ago). Frequencies of the Gm haplotype of 74 Chinese populations were compared with those of 33 populations from major racial groups. The results suggest that during human evolution, the Negroid group and Caucasoid-Mongoloid group diverged first, followed by a divergence between the Caucasoid and Mongoloid. Interrace divergence is high in comparison with intrarace divergence. There appear to be two distinct subgroups of Mongoloid, northern and southern Mongoloid. The northern and southern Mongoloid have Gm^1;21 and Gm^1,3;5 haplotypes as race-associate markers, respectively. Furthermore, the Caucasian-associated haplotype Gm^3;5 was found in several of the minorities living in the northwest part of China. The presence of the Gm^3;5 haplotype is attributed to the Caucasians living in Central Asia throughout the Silk Road. The amount of Caucasian admixture has been estimated. In contrast to the Gm haplotype distribution, Km¹ gene frequencies showed a random distribution in the populations studied.     

SF方案治疗肝硬化的疗效观察

目的：观察SF方案对代偿性乙型肝炎肝硬化患者的治疗作用。方法：代偿性乙肝肝硬化患者63例,分为治疗组33例,对照组30例。治疗组采用SF方案进行治疗,对照组采用常规护肝疗法,疗程为9～12个月,定期监测肝功能指标变化。结果：SF方案对肝硬化有较好的疗效,一是肝脏炎症反应减轻,肝功能恢复,血清ALT、AST、TBiL经治疗后治疗组均显著低于治疗前和同期对照组;二是阻止肝纤维化进展,肝纤维化指标明显好转;三是免疫功能得以改善,外周血CD4／CD8淋巴细胞比值回升,补体C3水平上升;四是抗病毒效果显著,HBVDNA阴转率达54．5％。结论：SF方案有显著改善患者肝功能,恢复患者免疫功能,抑制病毒增殖的作用,可扩大样本量进一步研究。     

Ferrochelatase gene mutations in erythropoietic protoporphyria: focus on liver disease.

A deficiency of ferrochelatase (FECH) activity underlies the excess accumulation of protoporphyrin that occurs in erythropoietic protoporphyria (EPP). In some patients, protoporphyrin accumulation causes liver damage that necessitates liver transplantation. The purpose of this study was to determine if specific mutations in the FECH gene are present in patients who develop liver disease. FECH cDNA and all 11 exons and their flanking intron regions in the FECH gene were amplified and sequenced by specific polymerase chain reactions. Gene mutations were determined in 34 individuals from 24 families: 14 had liver disease, 10 necessitating liver transplantation. All individuals were heterozygous for mutations that altered the coding region of FECH mRNA. The mutations in patients with liver disease were heterogenous, but usually caused a major structural alterations in the FECH protein, most commonly as a result of exon skipping in FECH mRNA. However, the mutations could not account for the severe phenotype by themselves, since the same mutations were found in asymptomatic family members of patients with liver disease and in patients from families in which liver disease was not present. Other genetic factors, and possibly acquired factors, also must be critical to the development of this severe phenotype in EPP.     

Gm(1) and Gm(2) immunoglobulin allotypes in patients with malignant melanoma.

Gm allotype markers were determined in sera from 71 melanoma patients and 400 control persons. There was no significant difference between both groups in Gm distribution. The results were compared to a recent report. Furthermore, in 25 malanoma patients the capacity of serum to interfere with cell-mediated cytotoxicity (CMC) of autologous lymphocytes was determined and related to the Gm allotype.