Nondialyzable Hexose of Human Synovial Fluid*†

Sandson, John; Hamerman, David

doi:10.1172/jci104095

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…The pathogenesis of rheumatic fever remains poorly understood, but is thought to involve stimulation by streptococcal antigens of antibodies cross-reactive with host tissues. Hyaluronic acid itself is poorly immunogenic, presumably because of its structural identity with the ground substance of mammalian cartilage (7,33). However, the presence of a capsular layer of hyaluronic acid may alter the antibody response to M protein or to other streptococcal products.…”

Section: Derivation Of a Nonmucoid Mutant Strain Of Gas By Tn916mentioning

confidence: 99%

Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

Wessels

Moses

Goldberg

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

332

275

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Mucoid strains of group A Streptococcus have been associated with recent outbreaks ofacute rheumatic fever. The mucoid colony morphology of these strains is a result of abundant production of capsular polysaccharide, which is composed of hyaluronic acid. To study the role of the hyaluronic acid capsule in virulence, we derived an acapsular mutant from a mucoid strain of group A Streptococcus by transposon mutagenesis. M protein expression was not altered in the mutant strain. The mucoid wild-type strain grew in fresh human blood and was resistant to phagocytic killing in vitro. In contrast, the acapsular mutant failed to grow in fresh human blood and was sensitive to phagocytic killing in vitro. Loss of capsule was associated with a 100-fold reduction in virulence of the organisms in mice. We conclude that the hyaluronic acid capsule protects mucoid group A streptococci from phagocytosis and has an important role in virulence.Group A Streptococcus (GAS) continues to be a major cause of morbidity and mortality throughout the world, both from infections and from the postinfectious sequelae of acute rheumatic fever and poststreptococcal glomerulonephritis. Recent reports suggest that after declining in frequency in developed countries for the past half-century, the incidence of life-threatening infections due to GAS and of acute rheumatic fever is increasing (1-5). The reasons for the resurgence of serious human diseases due to GAS are not known; however, it has been suggested that the GAS strains prevalent today may have increased expression of one or more virulence factors (1, 6). One such factor may be the hyaluronic acid capsule. Occasional strains of GAS isolated from clinical sources grow as large, spreading, wet colonies on solid media; this characteristic mucoid colony morphology is due to abundant production by these strains of the GAS capsular polysaccharide, which is composed of hyaluronic acid, a high molecular weight polymer consisting of alternating residues of N-acetylglucosamine and glucuronic acid (7,8). Mucoid strains of GAS have been implicated as causing unusually severe infections and frequently have been associated with individual cases or community outbreaks of rheumatic fever, including clusters of rheumatic fever cases reported recently from several regions of the U.S.A. (3, 5, 9, 10). Kaplan et al. (6) studied 42 GAS strains isolated from sibling contacts or patients with acute rheumatic fever during several outbreaks in the mid-1980s and found 45% to be mucoid.Mucoid isolates are generally rich in M protein and are highly virulent in experimental animals (9, 11). M protein has been considered to be the major surface component responsible for resistance of GAS to phagocytosis (12). The fact that highly virulent, M protein-rich strains usually appear mucoid suggests that the presence of a large hyaluronic acid capsule may also confer special virulence properties on these strains. Hirst (13) attempted to define the role of the hyaluronic acid capsule in virulence by experimentally in...

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Section: Derivation Of a Nonmucoid Mutant Strain Of Gas By Tn916mentioning

confidence: 99%

Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

Wessels

Moses

Goldberg

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

332

275

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“…Such a block would explain some of the abnormalities of mucopolysaccharide metabolism in rheumatoid arthritis (7)(8)(9)(10). Of these, the one discovered by Laskin, Engel, Joseph, and Pollak (8) is intriguing because it proved reversible by the administration of glucocorticoid hormones.…”

Section: Discussionmentioning

confidence: 99%

“…The postulate that abnormal manganese metabolism might be present in human collagen disease rests on the following: (a) Rheumatoid arthritis displays abnormalities of mucoprotein and mucopolysaccharide metabolism (7)(8)(9)(10); (b) Another collagen disease, the hydralazine syndrome, appeared linked to manganese deficiency on the basis of animal studies (11,12) ; (c) Induction of the hydralazine syndrome seems to depend upon the genetic substratum (13); and (d) Genetic factors may interact with environmental ones in the development of manganese deficiency, as was proven by the manganese-dependent defects of the pallid strain of mice (14,15).…”

Section: Introductionmentioning

confidence: 99%

Slow turnover of manganese in active rheumatoid arthritis accelerated by prednisone

Cotzias¹,

Papavasiliou²,

Hughes³

et al. 1968

J. Clin. Invest.

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Total body and area counts of intravenously injected 54Mn were measured periodically in 29 in-patients. A heterogeneous group of 19 control patients showed fair reproducibility in the immediate distribution, and considerable individual variance in the subsequent loss of the isotope. Eight studies of the effects of feeding excesses of manganous sulfate to five patients showed acceleration of the rate of loss of the radioisotope from the whole body and the liver. These findings seem compatible with the presence of control mechanisms in man, operating to vary the metal's excretion, while tending to preserve constancy of its concentration in tissues.Slow turnover rates of the metal were demonstrated in seven out of eight patients with active rheumatoid arthritis, in one with hydralazine disease, but not in one arthritic undergoing an impressive, spontaneous remission. Statistically significant differences were encountered in the measurements of 54Mn turnover of the total body, the thyroid, and the liver.Administration of prednisone induced clinical improvement and significant acceleration of these turnovers. Slow turnovers are characteristic of nutritional manganese deficiency. Therefore, serum and blood manganese determinations were performed by neutron activation analysis on 14 control patients, and on six patients with active rheumatoid arthritis. A statistically significant elevation of the red cell manganese concentration was encountered in patients with rheumatoid arthritis. This argued against the presence of classical trace-

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Acid phoshatase in human synovial fluid

Smith

Hamerman

1962

Arthritis & Rheumatism

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YNOVIAL MEMBRANE lining cells show acid phosphatase activity in S granules that are thought to be lysosomes.' In rheumatoid arthritis, the lining cells show markedly increased acid phosphatase activity.' This observation led us to compare acid phosphatase activity in synovial fluids from normal and arthritic joints with the thought that in rheumatoid arthritis, lysosome of lining cells might release their contained hydrolytic enzymes into synovial effusions. There appears to be no previous study of the occurrence of acid phosphatase in synovial fluid, although activities of a number of other enzymes have been measured: glucuronidase,2 pepsin and trypsin? amylase and lipase,' peroxidase,s alkaline phosphatase and transaminases8 METHODSPatients in the following groups were studied: 1) "Normal" subjects were those apparently free of joint disease. This group included Acid phosphatase (AP) activity was measured in synovial fluid from the knee, and in serum obtained at the same time. Three pleural fluids and three cerebrospinal fluids were also studied. All determinations were done within 30-60 minutes. The method of Andersch and Sczapinskis was used with paranitrophenyl phosphate (Sigma) as substrate. By this method the maximum normal level of serum AP is 0.63 units for males and 0.56 units for females.Cell counts and differential counts were carried out on synovial fluids within three hours after collection. Protein and hyaluronate determinations were done on most synovial fluids using methods described e1sewhere.S RESULTSOf six "normal" synovial fluids studied, four showed AP levels within normal limits, and two showed elevation of AP twice the maximum normal adult

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Nondialyzable Hexose of Human Synovial Fluid*†

Cited by 7 publications

References 12 publications

Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

Slow turnover of manganese in active rheumatoid arthritis accelerated by prednisone

Acid phoshatase in human synovial fluid

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