Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.     

Isolation and characterization of hemagglutinins from the sponge Dysidea herbacea

The sponge Dysidea herbacea (Keller) was found to possess hemagglutinins. The major component, DHA-I, is a protein with a mol. wt of 26,000, which dissociates into subunits of equal size (14,000). It contains large amounts of glutamic acid and aspartic acid residues, but no half-cystine, methionine or histidine residues. DHA-I reacted with rabbit and human AB0 erythrocytes. D-galactose and lactose were effective inhibitors of DHA-I. The sponge also contained a minor component(s) which reacted preferentially with rabbit erythrocytes but not with human AB0 erythrocytes.     

Differential sensitivity to tributyltin of cytochrome-containing and cytochrome-deficient cells of Escherichia coli SASX76

The effect of tributyltin (TBT) chloride on the growth of cytochrome-deficient and cytochrome-containing cells of Escherichia coli SASX76 was examined. The former cells were found to be at least 20 times more sensitive to TBT. It is proposed that the differential sensitivity of these two cell types to the biocide, TBT, may be due to a different mode of energy generation by cytochrome-deficient and cytochrome-sufficient cells. In addition to the energy state, the pH change caused by the presence and absence of cytochromes which occurred during growth also resulted in a differential sensitivity of these cells.     

A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16

Adult polycystic kidney disease (APCKD) is a common and often lethal multi-organ disease with an autosomal dominant pattern of inheritance; approximately 1 in 1,000 people carry the mutant gene. The major pathological abnormality is the development and progressive enlargement of cysts in several organs including the liver, pancreas and spleen as well as the kidneys. The basic biochemical defect which leads to the formation of cysts remains unknown. Cyst development, which is not retarded by any known therapy, leads to irreversible renal failure and death at a mean age of 51 unless dialysis or transplantation are used. Patients with the disease account for 9% of chronic dialysis requirement. The first symptoms tend to occur in the fourth decade, after most patients have reproduced. Presymptomatic diagnosis depends on the ultrasonographic detection of cysts, but exclusion cannot be achieved by this means; 34% of at-risk patients in the second decade and 14% in the third will go on to develop cysts after negative diagnosis. The low sensitivity of diagnostic techniques in this critical age-range imposes severe limitations on genetic counselling and the condition cannot be identified prenatally. Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05).     

Ringschlußversuche mit halogenierten Naphthalinthioglykolsäuren

Summary It has been found that cyclisation of -halogenated -naphthalene-thioglycolic acids can occur in -position with the elimination of the halogen. The influence of the temperature and of a further substituent (halogen) in the second nucleus are discussed.     

聚甲基乙撑碳酸酯的交联(英文)

利用过氧化物过氧化二异丙苯(DCP)和多官能团化合物三烯丙基异氰尿酸酯(TAIC),对聚甲基乙撑碳酸酯(PPC)进行了交联研究。研究发现, DCP和TAIC的用量对PPC的交联均有较大影响, PPC交联后,其凝胶含量、机械性能、弹性模量、玻璃化转变温度均有所增加, 1%的DCP和4%的TAIC用量可得到较理想的交联PPC材料。     

Chromosome 17-linked dementias

Chromosome 17-linked dementias have been defined by linkage analysis. The most common of these syndromes has been estimated to be the cause of between 2 and 20% of all dementia and has alternately been called frontotemporal dementia, Pick's disease (without Pick bodies) and dementia lacking distinctive features [1 – 3]. The identification of the mutation responsible for these conditions in a group of clinically and pathologically heterogeneous disorders may allow us to gain broad insight into the processes of neurodegeneration.     

Integrins and cardiovascular disease

Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor α _IIb  β ₃ , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of α _IIb  β ₃ inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system.