Myasthenia Gravis,Autoantibodies, and HL-A Antigens

The serum of 100 patients with myasthenia gravis and 441 of their first-degree relatives was studied for the presence of autoantibodies against several antigens. Antibodies to skeletal muscle were present in 22% of the patients and in 2% of the relatives. Both these frequencies were significantly higher than those in matched control subjects. Also, antinuclear antibodies were present more often both in the patients and in the relatives. Typing for HL-A antigens had shown a positive correlation between HL-A 8 and myasthenia gravis which was significantly higher in women than in men. Antibodies to skeletal muscle and thymomas were found to be much rarer in HL-A 8-positive patients than in HL-A 8-negative patients; HL-A 8-positive patients acquired the disease at an earlier age.HL-A 2-positive patients more often had thymomas and antibodies to skeletal muscle than HL-A 2-negative patients; HL-A 2-positive patients acquired myasthenia gravis at a later age.The fact that the clinical aspects of the HL-A 8-negative and HL-A 2-positive patients were different from those of the HL-A 8-positive and HL-A 2-negative patients justifies the hypothesis that there are two forms of myasthenia gravis.     

Histocompatibility Antigens in Active Chronic Hepatitis and Primary Biliary Cirrhosis

The frequency of antigens HL-A 1 (48%) and HL-A 8 (52%) in 54 patients with active chronic hepatitis from south-east England was significantly higher than in 89 control subjects from the same region (22% and 17% respectively). No correlation could be detected with the age and sex of the patients or with the presence of a particular immunological abnormality but the frequency of HL-A 1 and HL-A 8 was much lower in the nine patients who were positive for HBAg than in the 45 HBAg-negative cases. These results provide further evidence of the importance of genetic factors in active chronic hepatitis. In contrast the frequency of HL-A 1 and HL-A 8 in primary biliary cirrhosis, both in 45 patients from south-east England and in 28 patients from western Scotland, was not significantly different from that found in control groups from the same regions.     

慢性肾小球肾炎患者血清HGF、Cys-C、TAFI水平变化及其临床诊断价值

目的:分析慢性肾小球肾炎患者血清肝细胞生长因子(HGF)、胱抑素C(Cys-C)、凝血酶激活的纤溶抑制物(TAFI)水平的变化及其临床诊断价值。方法:选择我院2017年1月～2018年5月收治的71例慢性肾小球肾炎患者作为慢性肾小球肾炎组及同期于本院进行健康体检的83例作为健康对照组。检测进而比较两组血清HGF、Cys-C、TAFI水平,分析以上指标和患者肾功能的相关性及对慢性肾小球肾炎的诊断价值。结果:慢性肾小球肾炎组血清HGF、Cys-C、TAFI水平均显著高于对照组(P0.05)。慢性肾小球肾炎患者治疗后血清HGF、Cys-C、TAFI水平均显著低于治疗前(P0.05)。慢性肾小球肾炎患者血清HGF、Cys-C、TAFI水平和肾功能指标(肌酐(Scr)、尿素氮(BUN)、尿酸(UA))均呈显著正相关(P均0.05)。血清HGF水平诊断慢性肾小球肾炎的曲线下面积为0.826,敏感度和特异度分别为0.747和0.746;血清Cys-C水平诊断慢性肾小球肾炎的曲线下面积为0.821,敏感度和特异度分别为0.687和0.859;血清TAFI水平诊断慢性肾小球肾炎的曲线下面积为0.816,敏感度和特异度分别为0.855和0.647;血清HGF、Cys-C、TAFI水平联合检测诊断慢性肾小球肾炎的曲线下面积为0.951,敏感度和特异度分别为0.831和0.757。结论:慢性肾小球肾炎患者血清HGF、Cys-C及TAFI水平均明显升高,联合检测血清HGF、Cys-C及TAFI可能作为慢性肾小球肾炎诊断及预评估参考指标。     

Parenchymal destruction and arterial changes (haemodialysis intimal fibrosis) of glomerulonephritic kidneys in chronic intermittent haemodialysis.

The kidneys of 13 chronic diffuse glomerulonephritis patients who had been subjected to chronic intermittent haemodialysis were compared with those of 6 patients treated in the conservative way. Their renal parenchyma was examined with a semiquantitative histological method and advanced complete destruction of the glomeruli was demonstrated in the dialysed cases. There was no perceptive difference in the distribution of the various grades of damage of the recognizable glomeruli and tubules. With the exception of the chronic lobular glomerulonephritis cases, a marked obliterative mucoid intimal proliferation ("haemodialysis-intimal-fibrosis") had developed in the dialysed glomerulonephritis patients. It affected the renal arteries of all size from the segmental to the interlobular arties. Haemodialysis-intimal-fibrosis did not develop in the additionally examined 13 dialysed chronic pyelonephritis cases nor in 8 such treated conservatively. The change seems to be characteristic, but not specific, for chronic diffuse glomerulonephritis treated by chronic intermittent haemodialysis.     

Metabolomic identification of potential phospholipid biomarkers for chronic glomerulonephritis by using high performance liquid chromatography-mass spectrometry

Plasma phospholipids metabolic profile of chronic glomerulonephritis was investigated using high performance liquid chromatography/mass spectrometry (LC/MS) and principal component analysis. The plasma samples of 18 patients with chronic glomerulonephritis, 17 patients with chronic renal failure (CRF) without renal replacement therapy and 18 healthy persons were collected and analyzed. It was found that combination of the LC/MS technique with PCA can be successfully applied to phospholipid profile analysis. The results showed that primary chronic glomerulonephritis and CRF had phospholipids metabolic abnormality. Nineteen phospholipid species were identified as possible biomarkers in plasma samples of chronic glomerulonephritis and chronic renal failure. Moreover, the identification of the molecular structure of the potential phospholipid markers was obtained by ESI-MS/MS experiment. It suggests that phospholipids can be used as potential biomarkers on the progress of primary chronic glomerulonephritis.     

Polymorphic markers Val762Ala and Leu54Phe of the ADPRT1 gene associated with chronic glomerulonephritis in Russian patients from the city of Moscow

A comparative analysis of allelic and genotype distribution of polymorphic markers Val762Ala and Leu54Phe of ADPRT1 gene encoding poly(ADP-ribose)polymerase I has been performed in chronic glomerulonephritis patients compared to normal controls. This has shown a significant difference in the ADPRTI gene polymorphic marker Val762Ala allelic and genotype frequency distribution between chronic glomerulonephritis patients and healthy controls (according to Fisher's exact test). At the same time the allelic and genotype frequency for a polymorphic marker Leu54Phe distribution did not show significant difference between these groups. Therefore, we have concluded that the ADPRTI gene polymorphic marker Val762Ala is associated with the development of chronic glomerulonephritis in Russian patients of the Moscow region.     

Estimation of BetaIC Globulin in Glomerulonephritis

Serum beta_IC globulin, the third component of the complement system, was estimated by the single diffusion method (Oudin) and its significance in human glomerulonephritis was evaluated. This protein was depressed in two of three cases of acute proliferative glomerulonephritis and nine of 12 cases of acute glomerulonephritis. Beta_IC globulin continued to be low in two cases of active subacute glomerulonephritis whereas it returned to normal in five of the cases of acute glomerulonephritis. Values were normal in eight patients with membranous glomerulonephritis, four with chronic glomerulonephritis and one with hereditary glomerulonephritis, as well as in patients with other renal diseases and diseases of non-renal origin. In addition, levels were elevated in six patients with diseases of possible immune pathogenesis. It is concluded that beta_IC globulin estimation is a useful aid in the diagnosis and prognosis of glomerulonephritis in humans.     

Exclusion gene mapping utilizing patients with chromosome imbalance: the HL-A system as a prototype.

17 chromosomally unbalanced patients, their siblings and parents were tested for HL-A types and for up to 25 other polymorphic systems to determine whether there was gain or loss of an allele concurrent with the gain or loss of chromosome material. 5 patients had trisomy of part or all of a chromosome; 2 had trisomy of a segment and also deletion of chromosome material. All 7 were due to a familial translocation. The remaining patients had small deletions; 5 had ring chromosomes, 4 had rod deletions and 1 had missing chromosome material due to a heritable translocation. All cases were informative at the HL-A loci because of the high degree of polymorphism of the system whereas only some of the other systems were informative. None of the 17 patients showed unusual inheritance of HL-A or any other of the polymorphic systems examined. These results provide evidence excluding the HL-A and other loci from a number of possible locations in the human genome.     

Evidence for HL-A-linked genes in "juvenile" diabetes mellitus.

HL-A typing of 150 patients who had developed diabetes mellitus by the age of 30 years showed a significant association with HL-A 8 and W 15. The HL-A genotypes were determined in 17 families in which two or more siblings had this type of diabetes. The zygotic assortment of HL-A haplotypes was found to be significantly disturbed from the expected random pattern, with a reduction in the number of siblings showing no identical haplotypes and an appreciable increase in the number with both haplotypes identical. This appears to be most consistent with the presence of a gene or genes pre-disposing to this type of diabetes at a locus closely linked to the HL-A chromosomal loci. This locus appears to have a fundamental role in the susceptibility to juvenile diabetes.     

慢性肾小球肾炎患者血清MMP-9和TIMP-1的浓度及意义

目的:观察慢性肾小球肾炎血清基质金属蛋白酶9(matrix metalo protein-ase-9,MMP-9)、金属蛋白酶组织抑制剂1(tissue inhibitors of metalloproteinases,TIMP-1)的浓度与肾组织中MMP-9、TIMP-1表达的相关性,探讨慢性肾小球肾炎血清MMP-9、TIMP-1对肾脏纤维化的判断价值。方法:通过肾组织活检病理检查,将入选慢性肾炎的病例分增生组(A组)15例,纤维化组(B组)15例,另选10例志愿者作为健康对照组C组。应用免疫组化法观察A、B两组MMP-9、TIMP-1在肾组织中的表达情况,并且进行半定量分析,比较它们之间有无差别。应用ELISA双抗体夹心法检测A、B、C三组MMP-9、TIMP-1在血清中的浓度,比较它们之间有无差别。观察A、B两组MMP-9、TIMP-1在肾组织中的表达水平与在血清的浓度有无相关性。结果:A、B两组MMP-9在肾小球和肾间质少见表达,主要在肾小管上皮细胞浆中表达增高,两组之间表达的强度有显著差异性;A组TIMP-1在肾小球中少见表达,在肾小管上皮细胞增强。B组TIMP-1在肾小球中有少量表达,在肾小管上皮细胞较A组进一步增强,两组之间表达的强度有显著差异性(P0.05)。血清中MMP-9、TIMP-1浓度在A、B组显著高于C组,血清中MMP-9在A、B两组之间无显著差异性,血清中TIMP-1在A、B、C三组间两两比较有显著差别(P0.05)。结论:慢性肾炎患者血清中MMP-9、TIMP-1浓度与肾脏组织中MMP-9、TIMP-1的表达呈正相关。MMP-9、TIMP-1的相关性分析P值小于0.01。血清MMP-9、TIMP-1参与了肾脏纤维化的进展,慢性肾小球肾炎血清中MMP-9、TIMP-1的浓度可在一定程度上反映肾脏纤维化程度。     

Some biological properties of beta2-microglobulin and its antibody.

beta2-Microglobulin on the surface of lymphocytes exists in two molecular forms, first as part of the HL-A antigen complex, and second as a free molecule unbound to other membrane macromolecules. Quantitative determinations of the numbers of molecules of beta2-microglobulin per lymphocyte when compared to published values for the numbers of HL-A molecules per cell are consistent with an excess of beta2-microglobulin compared to HL-A antigens on the cell surface. Turnover studies of beta2-microglobulin from the lymphocyte surface indicated that both beta2-microglobulin and HL-A components are metabolized at similar rates. beta2-Microglobulin appears to be released in the free form. HL-A antigens, if released from the cell surface, appear to be released unbound to beta2-microglobulin. The effects of anti-beta2-microglobulin antibody on lymphocyte activation, namely on the mixed lymphocyte reaction and on antigen induced proliferative response, were studied. Anti-beta2-microglobulin completely inhibited the mixed lymphocyte reaction and the antigen induced proliferative response.     

C2 deficiency in man. genetic relationship to a mixed lymphocyte reaction determinant (7a*)

Three unrelated individuals with, respectively, lupus erythematosus, polyarteritis, and membranoproliferative glomerulonephritis and totally deficient in the second component of complement are demonstrated to be mutually poorly reactive in mixed lymphocyte culture and homozygous for the mixed lymphocyte reaction determinant (MLR-S or LD) short 7a (7a^*). The gene controlling the elaboration of C2 in man is shown to be separate from, and probably to map outside of, the second locus ofHL-A and theMLR-S locus. Genetic linkage disequilibrium is strongly suggested between HL-A 10, W18, 7a^*, and C2 deficiency.     

Purification of papain-solubilized histocompatibility antigens from a cultured human lymphoblastoid line, RPMI 4265.

HL-A antigens having specificities HL-A2, HL-A7, HL-A12 have been solubilized by papain treatment of membrane preparations from the cultured human lymphoblastoid cell line RPMI 4265 and purified about 80-fold by chromatography on carboxymethylcellulose, Sephadex G-150, and diethylaminoethylcellulose columns. Separation of HL-A2 from a mixture of HL-A7 and HL-A12 was achieved on the final DEAE-cellulose column. The yield was about 1 mg of protein of each antigen preparation per 100 g of packed, frozen cells. On sodium dodecyl sulfate gel electrophoresis both preparations showed two polypeptide bands. The smaller subunit of 12,000 daltons is common to all HL-A preparations and has been shown to be identical with beta2-microglobulin. The larger subunit is a glycopeptide and in the HL-A7, 12 preparation was resolved into a duplex of 34,000 and 37,000 daltons. The HL-A2 preparation showed a single band at 34,000 daltons. On isoelectric focusing under nondenaturing conditions, the preparation showed multiple bands, all of which contained both subunits and retained antigenic activity. On isoelectric focusing in the presence of 6 M urea a single band for beta2-microglobulin and multiple bands for the larger subunit were seen. This charge heterogeneity of the larger subunit has been shown to be due to variable amounts of sialic acid. When HL-A antigen preparations were subjected to Sephadex G-100 chromatography in the presence of 3 M KCl, no separation of the two subunits was observed.     

血清胱抑素C和尿微量白蛋白在慢性肾小球肾炎早期肾功能损害评估中的意义

目的:探讨血清胱抑素C和尿微量白蛋白在慢性肾小球肾炎早期肾功能损害评估中的意义。方法:选取2010年9月至2013年7月我院收治的86名慢性肾小球肾炎患者,设为观察组。另选取同期在我院体检的年龄、性别等资料与之匹配的66名健康者设为对照组。分别对患者的CysC以及mALB的含量进行测定,并进行统计分析。结果:观察组和对照组的Cys C含量分别为(2.68±1.19)mg/L、(0.83±1.04)mg/L,观察组明显高与对照组;mALB的含量观察组为(38.16±4.25)mg/L,相比于对照组的(6.87±3.93)mg/L明显升高;Cys C及mALB阳性指标的检出率分别为75.58%、76.74%,而Cys C与mALB进行联合检测,检出率为91.86%,相比于单指标的检出率明显提高。差异具有统计学意义(P0.05)。通过对慢性肾小球肾炎患者的两项指标进行相关性分析,发现血清Cys C和尿mALB的含量呈显著的正相关(r=0.941,P0.05)。结论:将CysC与mALB相结合检测用以对慢性肾小球肾炎患者早期肾功能损害进行评估,检出率和敏感性均明显高于单指标检测。     

Polymorphic markers <Emphasis Type="Italic">Val762Ala</Emphasis> and <Emphasis Type="Italic">Leu54Phe</Emphasis> of the <Emphasis Type="Italic">ADPRT1</Emphasis> gene associated with chronic glomerulonephritis in Russian patients from Moscow

A comparative analysis of allele and genotype distribution of polymorphic markers Val762Ala and Leu54Phe of ADPRT1 gene encoding poly(ADP-ribose)polymerase1 has been performed in chronic glomerulonephritis patients compared to normal controls. This has shown a significant difference in the ADPRT1 gene polymorphic marker Val762Ala allele and genotype frequency distribution between chronic glomerulonephritis patients and healthy controls (according to Fisher’s exact test). At the same time the allele and genotype frequency for a polymorphic marker Leu54Phe distribution did not show significant difference between these groups. Therefore, we have concluded that the ADPRT1 gene polymorphic marker Val762Ala is associated with the development of chronic glomerulonephritis in Russian patients of the Moscow region.     

Leukolysis reaction in the diagnosis of allergy to antibacterial preparations in pulmonology]

The experiment included 109 patients with non-specific pathological processes in the lungs. i.e. 21 cases with acute and 55 cases with chronic pneumonia and 33 cases with bronchial asthma with or without chronic pneumonia. Clinically intolerance of the antibacterial drugs was observed in 39 patients and increased leucolysis (above 15 per cent) was observed sometimes more frequently. Only with the use of penicillin the difference was 1.6 times. Out of 39 patients with clinical signs of allergy to antibiotics or sulphanilamide only 20 showed the signs of increased leucolysis on the use of the respective drug. No correlation between the percentage of the leucolysis cases due to antibiotics or sulphanilamides and the clinical signs of their intolerance was observed. The use of such drugs by a person or even only his presence in the hospital often induced increased leucolysis which may be considered as an indication of the person sensibilization to them.     

Die Genetik des HL-A-Systems

Zusammenfassung Die Analyse der Gewebstypen von 300 nichtverwandten Personen der österreichischen Bevölkerung und von 110 Familien mit 381 Kindern, die erstmals in diesem Umfang vorgenommen wurde, bestätigt die formalgenetische Hypothese der Vererbung des HL-A-Systems. Dieses System wird über 2 eng gekoppelte Loci eines Autosoms, den LA- und den 4-Locus, gesteuert, wobei an beiden Loci multiple Allelie vorliegt und die einzelnen Merkmale einen dominanten Erbgang aufweisen. Die Genfrequenzen der HL-A-Gene und die Haplotypenfrequenzen wurden errechnet. Die Häufigkeit der Rekombinationen innerhalb des HL-A-Systems wurde mit 0.38% ermittelt. Es wurde kein Anhaltspunkt für eine Selektion bei der Vererbung der HL-A-Merkmale gefunden. Basierend auf den formalgenetischen Untersuchungen wurde die Brauchbarkeit (Vaterschaftsausschlußchance) und die Wertigkeit (Beweiswert) des HL-A-Systems diskutiert. Zur Berechnung der Vaterschaftsausschlußchance wurde eine Formel, die das Koppelungsungleichgewicht der 2 Loci des HL-A-Systems berücksichtigt, entwickelt.

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The genetics of the HL-A-System A study of population and families and its application in paternity cases

Summary 300 unrelated individuals of the Austrian population and 110 families with 381 children have been typed by means of the microlymphocytotoxic test. The analysis of the results of this study shows that the HL-A-antigens are governed by 2 closely linked loci of an autosomal chromosome, the LA-locus with the genesHL-A1, HL-A2, HL-A3, HL-A9, HL-A10, HL-A11, Ba ^*,Li and the 4-locus with the genesHL-A5, HL-A7, HL-A8, HL-A12, HL-A13, R ^*,BB, FJH, MaKi, AA, MaPi, LND andET. Further, it was found that there must exist more antigens, which are not yet serologically detectable, within both loci. The genes of the HL-A-system are inherited as codominant characters. The gene frequencies of the individual determinants and the haplotype frequencies are calculated. The recombination frequency within the HL-A-system was found to be 0.38%. No evidence with regard to a selection could be recognized analysing the inheritence of the HL-A-genes. Basing on the genetical analysis, the efficiency of the HL-A-system in paternity cases is discussed. The chance of exclusion in false accusations of paternity was calculated by means of a formula developed for this purpose, which takes into account the linkage disequilibrium between the LA- and the 4-locus, and was found to be approximatively 76%.

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National Blood Group Reference Laboratory (WHO), National Tissue Typing Reference Laboratory (Council of Europe).     

Failure of renal dopamine response to salt loading in chronic renal disease.

Eight patients with chronic glomerulonephritis and five age-matched normal volunteers were given additional sodium chloride by mouth under conditions of metabolic balance. Whereas in the normal volunteers plasma renin activity was suppressed and urinary excretion of free dopamine increased, in the patients dopamine was not mobilised and plasma renin activity was not completely suppressed. Abnormal retention of sodium and water in glomerulonephritis may be due partly to a failure to mobilise dopamine in the kidney. Specific renal dopamine agonists may be natriuretic and hypotensive in chronic glomerulonephritis.     

Selective effect of low protein diets in chronic renal diseases.

It has recently been established that the rate of progression of chronic renal failure in man can be slowed by restricting dietary protein. Consequently, the short term and long term effects of a low protein diet on the course of different chronic nephropathies were studied in an attempt to delineate the factors that determine the response to such a diet. When a low protein diet was given for six months renal function improved significantly in nine patients with chronic tubulointerstitial nephritis (p less than 0.025); the diet had a marginally beneficial effect in 12 patients with chronic glomerulonephritis (p less than 0.05) and no effect in nine with hypertensive nephrosclerosis. The heterogeneous functional response in the patients with chronic glomerulonephritis correlated closely with the effect of the diet on these patients'' proteinuria (r = 0.76, p less than 0.01). In a short term study (four weeks) of 12 patients with chronic renal failure changes in renal plasma flow were proportional to dietary protein intake. Renal vascular resistance fell during a high protein diet and increased when dietary protein was restricted. The changes in renal plasma flow during the low protein diet correlated well with the patients'' long term functional response to the diet (r = 0.76, p less than 0.01). It is concluded that the response to a low protein diet in chronic renal failure is determined, firstly, by the nature of the underlying nephropathy, with maximal benefit being observed in non-glomerular disorders; secondly, by the effect of the diet on the proteinuria in chronic glomerulonephritis; and, thirdly, by the haemodynamic response to the diet, with patients with a reactive renal vascular bed improving with a low protein diet.