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Light and electron microscopy of rabbit testes infected with Treponema pallidum (Nichols strain): nature of deposited mucopolysaccharides and localisation of treponemes.

The mucopolysaccharide nature of the material deposited in rabbit testes infected with Treponema pallidum was confirmed by histochemical staining with alcian blue. Differential staining of mucopolysaccharides showed the presence of sulphated mucopolysaccharides as an almost constant feature, whereas in little more than half of the orchitic testes studied variable deposits of hyaluronic acid were seen. The treponemes were almost exclusively present in the areas rich in mucopolysaccharide. A combination staining with the Warthin-Starry method and alcian blue showed treponemes in close association with pre-existing fibrils and cells contained in these fibrils. The latter findings were confirmed by electron microscopy, and the fibroblasts to which treponemes adhered displayed the characteristics of activated cells. The close parallel between the histopathological changes observed here and their descriptions in published reports shows that our specific strain still behaves the same as the original Nichols pathogenic strain of T pallidum.

Animals↗

Ground substance mucopolysaccharides and plasma proteins: their role in capillary water balance.

The osmotic interaction of mucopolysaccharides and plasma proteins, normally present in the interstitium, has been investigated. It has been found that hyaluronate-plasma protein mixtures may be treated as a two-phase system and that the two phases are in osmotic equilibrium. The osmotic pressures exerted by these mixtures are higher than the algebraic sum of the two components. At concentrations normally present in the interstitium of skin and muscle (0.6% mucopolysaccharides and 2% protein), the osmotic pressure exerted by the mixture is on the order of 10 mmHg, which is in agreement with predictions from earlier computer-simulation studies. The partition of fluid between the gel-like mucopolysaccharide compartment and the free-fluid containing the protein is approximately 50% in the "gel" phase at concentrations found in the interstitium. The volume exclusion effects of the interstitial mucopolysaccharides are significant, both in terms of selection of tracer molecules for interstitial volume measurements and also as an osmotic buffering mechanism which aids in maintaining the partition of fluid between the circulation and the interstitial space.

Blood Proteins↗

Acid mucopolysaccharides in mammary tumors of dogs.

The predominant acid mucopolysaccharides found in selected epithelial mammary tumors of dogs stained with alcian blue and were labile to hyaluronidase digestion. These histochemical characteristics identified them as hyaluronic acid, chondroitin-4- and chondroitin-6-sulfate. The intensity of the staining of these acid mucopolysaccharides varied in a transitionary process from a precartilaginous to a pseudocartilaginous intercellular matrix to mature hyaline cartilage. The tumor acid mucopolysaccharides were indistinguishable from those associated with formation of cartilage in developing mammals; such cartilage is reported to be produced only by cells of mesodermal origin. There was no evidence to suggest transitional changes in myoepithelial cells, neoplastic epithelial cells or their components that could contribute to the formation of the acid mucopolysaccharides. It was concluded that the heterotopic tissues (cartilage, bone and fibrous connective tissue) in the epithelial mammary tumors were derived from cells of mesodermal origin and formed the adjacent stroma in areas of neoplasia.

Animals↗

Enzyme replacement therapy for the mucopolysaccharide storage disorders.

The mucopolysaccharide storage disorders are a group of lysosomal storage disorders associated with deficiencies of lysosomal enzymes required for the normal sequential degradation of glycosaminoglycans, formerly known as mucopolysaccharides. The accumulation of glycosaminoglycans in a wide variety of tissues results in a complex and progressive disease leading to death in the first or second decade in most patients. Studies of enzyme replacement in animal models of mucopolysaccharide disorders have demonstrated the potential of parenterally administered enzyme to reduce glycosaminoglycan storage and microscopic pathology. Clinical studies of enzyme replacement therapy are currently underway for mucopolysaccharidosis I, mucopolysaccharidosis VI and mucopolysaccharidosis II. The complexity and heterogeneity of the mucopolysaccharide disorders provide significant challenges for clinical study design and evaluation. Innovative clinical development strategies may be needed to lower the development cost and time for complex rare disease therapies to assure that such patients receive therapies they deserve.

Animals↗

The use of double staining techniques for investigating bacterial attachment to mucopolysaccharide-coated epithelial cells.

Double staining techniques were devised to study Escherichia coli attachment to mucopolysaccharide-coated urinary tract epithelial cells. In addition, vital stains were used to distinguish between viable and nonviable epithelial cells. Alcian blue was used to confirm the presence of glycosaminoglycans and periodic acid Schiff was used to distinguish a further group of polysaccharides, proteoglycans, neutral mucosubstances and glycolipids. The staining methods enabled investigations to be carried out concerning the possible importance of mucopolysaccharides in the attachment of bacteria to mucosal surfaces. Staining techniques were also used to investigate whether the presence of a mucopolysaccharide coat is related to epithelial cell viability. The combinations of vital and mucopolysaccharide stains were found to give reproducible results when cell preparations were evaluated by three individuals. Both in vivo and in vitro certain populations of epithelial cells have been found with a large number of bacteria preferentially attached. The double staining techniques described here may help to reveal the nature of these target cells.

Adhesiveness↗

Cytochemical localisation of lysosomal enzymes and acidic mucopolysaccharides in the salivary glands of Aplysia depilans (Opisthobranchia).

Three types of secretory cells were reported in the salivary glands of Aplysia depilans: granular cells, vacuolated cells and mucocytes. To improve the characterisation of these cells, cytochemical methods for the detection of lysosomal enzymes and acidic mucopolysaccharides were applied. In granular cells, acid phosphatase and arylsulphatase were present in small lysosomes and in some secretory granules. The secretory granules could have received these enzymes after fusion with the small lysosomes that were frequently found very close to them. These cells were not stained with colloidal iron because they do not contain acidic mucopolysaccharides. In vacuolated cells, acid phosphatase and arylsulphatase were detected in lysosomes but not in the secretory vacuoles. Colloidal iron staining revealed the presence of acidic mucopolysaccharides in the vacuoles and in the Golgi apparatus of these cells. In mucocytes, lysosomes were very rare, but the secretion of these cells was very rich in acidic mucopolysaccharides. The filamentous network within the secretory vesicles was completely covered with iron particles, but practically no particles were observed over the granular masses attached to the membrane of the vesicles. Iron particles were also found in the trans-face cisternae of the U-shaped Golgi stacks, but were not seen in the cis-face cisternae or in the rough endoplasmic reticulum.

Acid Phosphatase↗

Degree of sulfation in mucopolysaccharide sulfates in normal and stone-forming urines.

Mucopolysaccharides were extracted from both normal and stone-forming urines, and those from the stone-forming samples showed a higher degree of sulfation than those from normal urines, as determined by sulfate analysis and electrophoretic measurement. The sulfated mucopolysaccharides from stone-forming urines formed insoluble calcium salts, whereas those from normal urines generally remained soluble in the presence of calcium ion. Rachitic rat cartilage was found to have more highly sulfated mucopolysaccharides than normal rat cartilage. Highly sulfated mucopolysaccharides appear to be a significant factor in calcium stone formations.

Animals↗

[Mucopolysaccharide content in the wool of sheep of different breeds].

The content of acid mucopolysaccharides was studied in wool from sheep of different species. In particular it was shown that the wool of fine fleece sheep is notable for the highest content of mucopolysaccharides. A comparatively lower quantity of mucopolysaccharides was found in the woold of hair sheep. The content of mucopolysaccharides in wool is closely connected with it structure; i.e. with the ratio of individual keratoses in it.

Animals↗

[Effect of age on the urinary excretion of mucopolysaccharides].

Content of mucopolysaccharides was studied by a test for hexuronic acids and hexosamines in day urine of men and women at the age of 20-80, and older. Mucopolysaccharides were precipitated with ethanol. In urine content of mucopolysaccharides was slightly increased up to the age tof 40-54 and later on it was decreased. Content of acid mucopolysaccharides was lower in urine of women aged 20-29 than in urine of men of the same age group.

Adult↗

Distribution of mucopolysaccharides and glycoproteins in the articular discs of temporomandibular joints in human fetuses.

AIMS: To evaluate the distribution of mucopolysaccharides and glycoproteins in the articular discs of temporomandibular joints (TMJs) in human fetuses at different stages of development in order to test the hypothesis that the development and histological maturation of the articular disc has already begun by the 12th week of gestation. METHODS: Eighteen human fetuses at gestational ages 12, 14, and 16 weeks were used (6 fetuses of each age). Sections (6 microm wide) of the articular discs were stained with trichromic stain for collagen fibers, Mayer's mucicarmine for mucopolysaccharides, and Schiff's periodic acid reaction for glycoproteins. The densities of the stained zones were measured by means of Image J software. The nonparametric Kruskal-Wallis test was used to evaluate the differences among stained zones in the 3 fetus groups. RESULTS: TMJ tissues of four of the six 12-week-old fetuses were stained positive for collagen fibers, mucopolysaccharides, and glycoproteins. In these fetuses the stain was localized to the articular posterior area and was denser in that area than in the middle and anterior areas. The stained areas in the 14-week-old fetuses were distributed throughout the articular discs, with isolated clear unstained areas. The stained areas of all the articular discs of the 16-week-old fetuses were more compact than those of the 12-and 14-week-old fetuses. In all the fetuses examined, the collagen fibers along the articular disc had a wavy appearance. The fossa of the temporal bone was observed in all the fetuses as a straight structure that was similar in the 3 fetus groups. The densities (mean +/- SD) of the stained zones were 38.36% +/- 3.39%, 59.5% +/- 1.56%, and 94.04% +/- 2.04% for 12, 14, and 16 weeks of gestation, respectively; these densities were significantly different (chi2 = 15.16; df = 2, P < .001). CONCLUSION: This study indicates that mucopolysaccharides and glycoproteins as well as collagen fibers are present at 12, 14, and 16 weeks of gestation. This suggests that the histological maturation of the articular disc has already begun at the 12th week and is complete by the 16th week of gestation.

Fetal Development↗

Heritable disorders of mucopolysaccharide metabolism.

The heritable diseases of mucopolysaccharide metabolism have undergone reclassification during the past several years as a result of advances in knowledge. Recognition of clinical, genetic and biochemical differences has made it possible to delineate six types of mucopolysaccharidosis. All types are characterized by excessive excretion of one or more acid mucopolysaccharides in the urine. The underlying defect is not known at present, but recent investigations have suggested possible defects in protein binding and increased biosynthesis and storage of the various mucopolysaccharides. Treatment of these disorders has been unrewarding, although administration of corticosteroids may be of some benefit.Several diagnostic tests are now available for the determination of excessive urinary acid mucopolysaccharide excretion.

Carbohydrate Metabolism, Inborn Errors↗

Acid mucopolysaccharides in leprosy lesions.

Uniform accumulation of acid mucopolysaccharides in all types of leprosy lesions was seen, except late tuberculoid lesions which showed the accumulation only at the periphery. Absence of acid mucopolysaccharides was significant in well formed epithelioid granulomas and in giant cells of late tuberculoid cases. Generally a progressive decrease with advancing chronicity of the disease was noted. The dermal zone without any cellular infiltrate showed abundant acid mucopolysaccharides in comparison to those areas having inflammatory cell infiltrate in 70.83% of LL, 42.86% of BL, 33.3% of BB, 40.0% of BT, and 13.51% of TT cases. In Indeterminate cases the distribution was same to that of control cases. Testicular hyaluronidase digestion established that hyaluronic acid constituted the main bulk of acid mucopolysaccharides. The possible source of hyaluronic acid is discussed.

Adolescent↗

The role of mucopolysaccharide induction in treatment of experimental osteoarthritis in rats by ultrasound.

Therapeutic ultrasound has been used in the treatment of osteoarthritis for the relief of symptom and improvement of functional status. In recent study, we found that ultrasound enhances cartilage repair in experimental early stage osteoarthritis, and prevents deteriorative changes in later stages. In the present study, we further investigate the bioeffects of ultrasound on cartilage matrix of experimental arthritis. Fifty-four rats with three different degrees of papain induced osteoarthritis classified by 99m-Tc pertechnetate bone scan were collected for ultrasound treatment. The changes in their arthritic severity after sonication treatment and two months after treatment were measured using 99m-Tc bone scan. The histopathological changes were evaluated through light microscope after disarticulation sections (H.E. stain), and the changes in mucopolysaccharide density in cartilage matrix were measured using a Optimas scanner analyzer after Alcian blue staining. The results showed that the density of mucopolysaccharide rose in the initial stage of induced arthritis, and decreased progressively in the later stage. The density of mucopolysaccharide increased upon complete sonication more for the treated rats than for the controls, and this was closely related with the improvement in histopathological findings, but inversely with the changes in arthritic severity. In conclusion, therapeutic ultrasound enhances mucopolysaccharide synthesis of arthritic cartilage, and results in the repair of arthritic cartilage in the early stage of induced arthritis and the prevention of deteriorative changes in later stages.

Animals↗

METABOLISM OF ACID MUCOPOLYSACCHARIDES.

The biosynthesis of the acid mucopolysaccharides, hyaluronic acid and chondroitin sulfuric acid, occurs by way of uridine nucleotides which contain the monosaccharide units of the respective polysaccharides. The mechanism of alternation of groups is as yet unknown. Certain of the acid mucopolysaccharides are covalently bound to protein by way of serine. In the case of the protein-polysaccharide complex of cartilage, there is evidence to suggest that the polysaccharide may be linked to the serine by way of galactose. Chondroitin sulfuric acid B may be isolated almost free of amino acids from the tissues and urine of patients with the Hurler syndrome without the use of proteolytic enzymes, acid, or alkali. This contrasts markedly with the tight binding of this compound to protein in normal tissue. It is suggested that the metabolic defect in this disease may reside in a defect of the peptide or linkage of the peptide to polysaccharide resulting in failure of the acid mucopolysaccharide to be fixed normally in connective tissue. Such a defect may result in interference with normal regulation of polysaccharide synthesis with a resultant increased synthesis. It is proposed that such a mechanism may obtain in other heritable connective tissue diseases as well as other storage diseases.

Carbohydrate Metabolism↗

Inhibition of mucopolysaccharide sulfation.

A method of measuring the inhibition of sulfation in mucopolysaccharides employed the coupled enzyme system of Wortman. This procedure utilized the phenol and mucopolysaccharide sulfotransferases of beef cornea extract. Compounds tested against this system included amino acids, salicylates, 2-mercaptoethylamine and a derivative, heterocyclic ethanethiosulfuric acids, arylsulfonamidoethanethiosulfates, and several other compounds. In general, the salicylates and thiosulfates were inhibitory, with sodiumm 2-(4-acetamidobenzenesulfonamido)-ethanethiosulfate being the most inhibitory and 2-mercaptoethylguanidine trithiocarbonic acid the second most inhibitory. Salicylamide and allopurinol, which have been employed in kidney stone therapy, were inhibitors. Kidney stones have a mucopolysaccharide sulfate matrix, which is involved in their growth.

Animals↗

Immunologic and chemical studies on mucopolysaccharide derived from murine lymphosarcoma.

Mucopolysaccharide was prepared from media in which the Gardner's lymphosarcoma cells were cultured. Multiple intraperitoneal injections of the preparation into syngeneic mice resulted in enhancement of the tumors which were inoculated prior to the injections. Sera of these hosts contained antibodies reacting with antigens of the outer layer of the tumor cells. Chemical analyses of the preparation showed that the mucopolysaccharide is composed of hexosamine, uronic, acid, hexose, and proteins. The mucopolysaccharide was shown to possess unique migration rate on electrophoresis and thin layer chromatography.

Animals↗

In vivo synthesis of acid mucopolysaccharides by Ehrlich ascites tumor cells.

The biosynthesis and intracellular distribution of acid mucopolysaccharides in Ehrlich ascites tumor cells was studied in vivo by means of the precursors 35S-sulfate, 3H-glucosamine and 14C-galactosamine. It was found that the acid mucopolysaccharide present in the ascitic fluid supernatant is hyaluronic acid. Hyaluronic acid appears to be of extracellular origin, and it is bound to proteins of the cell membrane. The ascites cells exhibit a very active production of sulfated mucopolysaccharides particularly at the mitochondria and cell membrane level. Chondroitin sulfate A is the major component but also the isomers B and C are present. The possible role of chondroitin sulfate A in the development of neoplastic characteristics of the cell is discussed.

Animals↗