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Increased urinary excretion of acid mucopolysaccharides and glycopeptides in hypothyroidism following thyroid hormone therapy.

Urinary excretion of acid mucopolysaccharides and glycopeptides in the urine of an untreated patient with cretinism were measured before and after thyroid hormone replacement. Urinary uronic acid and hexose excretion in the CPC-precipitated fraction increased four to ten times after thyroid hormone administration. The maximum excretion was observed after 2 months of thyroid replacement. The excreted acid mucopolysaccharides consisted of chondroitin sulphate A/C and minor quantities of heparan sulphate. Urinary excretion of glycopeptides, particularly small molecular glycopeptides rose also four to five-fold with thyroid hormone administration. These data suggest that thyroid hormone markedly influences the metabolism of acid mucopolysaccharides and glycoproteins. Possibly, the lack of thyroid hormone caused a decreased activity of various lysosomal glycosidases and sulphatases.

Child↗

Detection of acid mucopolysaccharides in human brain tumors by histochemical methods.

Acid mucopolysaccharides (glycosaminoglycans) are identified by histochemical methods in biopsies of 107 human brain tumors. Isomorphous oligodendrogliomas and astrocytomas stained with alcian blue show marked, weblike, or diffuse distribution and concentration of acid mucopolysaccharides. Histochemically, the characteristics of hyaluronic acid and chondroitin sulphate are found. They seem to be closely associated with the cytoplasmic membrane of the tumor cells. Increased dedifferentiation and malignancy lead to a progressive loss of alcianophilia. In tumors such as ependymomas, meningiomas, sarcomas, and medulloblastomas, concentration of alcian blue is found only in the blood vessel walls and connective tissue. In neurinomas a greater amount of acid mucopolysaccharides can be shown not only in the collagen fibers but also in tumor areas of the Antoni-B-type. One case of cerebral neuroblastoma revealed marked alcianophilia of the parenchyma and stroma. As with findings in experimental brain tumors, an altered regulation of the carbohydrate metabolism of the glia cells during neoplastic transformation is discussed as a reason for the alcianophilia of gliomas.

Astrocytoma↗

Echocardiographic abnormalities in the mucopolysaccharide storage diseases.

The mucopolysaccharide storage diseases express themselves clinically with a wide variety of abnormalities, including growth and mental retardation, skeletal abnormalities, clouded corneas, nerve compression syndromes, upper airway obstruction and cardiovascular involvement, to name the most common. In most cases the cause of early death is cardiorespiratory failure secondary to cardiovascular involvement and upper airway obstruction. The findings of cardiac ultrasound examination in 29 children, adolescents and young adults are presented. In addition to the previously well-described abnormalities of the mitral and aortic valves in several types of mucopolysaccharide storage disease, we report patchy involvement in some cases, 3 instances of asymmetric septal hypertrophy not previously reported in mucopolysaccharide storage diseases, cardiac involvement in half of our patients with Sanfilippo syndrome and a lack of age-related severity of cardiac involvement even within the specific syndromes.

Adolescent↗

Corneal clouding with increased acid mucopolysaccharide accumulation in Bowman's membrane.

Two infants had bilateral congenital corneal clouding and abnormal acid mucopolysaccharide accumulation in a thickened Bowman's membrane. This unusual entity was not associated with acid mucopolysaccharide deposits in the skin and visceral tissues or with increased levels of acid mucopolysaccharide in the urine. The similarity and differences have been compared to the systemic mucopolysaccharidosis and macular corneal dystrophy.

Basement Membrane↗

Differentiation of mucopolysaccharidoses by analyses of the excreted sulfated mucopolysaccharides.

Analyses of sulfated mucopolysaccharides excreted by patients with Hunter, Hurler, Scheie, Sanfilippo A and Sanfilippo B syndromes are reported. Three distinct methods, namely agarose gel electrophoresis, enzymatic degradation and molecular weight determination, were used in an attempt to differentiate the mucopolysaccharidoses by analysis of the urinary mucopolysaccharides. It is shown that by the combination of these methods it is possible to differentiate most of the syndromes and also to demonstrated that some patients with the same syndrome excrete different types of sulfated mucopolysaccharides.

Diagnosis, Differential↗

Tissue specific distribution of sulfated mucopolysaccharides in mammals.

A comparative study on the distribution of sulfated mucopolysaccharides in several tissues of five mammalian species is reported. It is shown that each tissue has a characteristic composition differing from each other regarding the relative amount, type and molecular size of chondroitin sulfate A/C, chondroitin sulfate B and heparan sulfate. It is also shown that the same tissue from different mammals has the same types and proportions of sulfated mucopolysaccharides, but with different molecular weights. Exception to this rule was observed for the distribution of heparin which was present only in a few tissues of the five mammals studied. The possible involvement of the sulfated mucopolysaccharides in cell recognition and/or adhesiveness is discussed in view of this characteristic distribution.

Animals↗

Selective exposure of mucopolysaccharides is involved in macrophage physiology.

Surface and intracellular mucopolysaccharides of guinea-pig peritoneal macrophages maintained in suspension and monolayer culture were studied. At least five classes of compound (hyaluronic acid, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate and chondroitin 6-sulfate) were resolved and characterized by electrophoresis and enzymatic degradation. The results reported here suggest that modulation of mucopolysaccharide exposure is involved in macrophage physiology. The possible biological role of surface mucopolysaccharides in macrophage activity is discussed.

Animals↗

Identification of acidic mucopolysaccharides by agarose gel electrophoresis.

A micro-method for the identification of most acidic mucopolysaccharides by agarose gel electrophoresis with three different buffer systems is described. In barbital buffer the mucopolysaccharides are fractionated from each other as a function of their net charge, whereas in a diamine buffer the fractionation is probably achieved according to the degree to which they are bound to the diamine. A combination of barbital and diaminopropane buffers in two-dimensional electrophoresis for the identification of mucopolysaccharides is also described.

Electrophoresis, Agar Gel↗

Species of 67Ga-binding acid mucopolysaccharide in liver.

It was determined from measuring neutral saccharide in the structure that the principal 67Ga-binding acid mucopolysaccharide in liver was keratan sulfate and/or keratan polysulfate. On the other hand, it was clarified from the results of mucopolysaccharase treatment that the main 67Ga-binding acid mucopolysaccharide in liver was not either one of keratan sulfate, heparan sulfate, heparin, chondroitin sulfate A, B and C. Based on the present results, it was deduced that the main 67Ga-binding acid mucopolysaccharide in liver was keratan polysulfate.

Animals↗

Histochemical reactions for mucopolysaccharides in the dinosaur bone. Studies on Epon- and methacrylate-embedded semithin sections as well as on isolated osteocytes and ground sections of bone.

The dinosaur bone was examined with the aim to detect in it the presence of mucopolysaccharides. The methacrylate- and Epon-embedded semithin sections of the studied bone were found to contain substances giving positive reaction on application of histochemical procedures used for identification of mucopolysaccharides (mucosubstances). These substances were also shown to be localized in the perivascular space, within the vascular canal, and around the osteocytes. The distribution of mucopolysaccharides in the dinosaur bone turned out to be comparable with their distribution in the bones of contemporary animals.

Animals↗

Selective interaction of a Fucus vesiculosus lectin-like mucopolysaccharide with several Candida species.

A complex carbohydrate specific lectin-like mucopolysaccharide extracted from the brown alga Fucus vesiculosus was found to agglutinate Candida guilliermondii cells but not those of other species of the same genus (except for a weak agglutination with C. krusei). The selective binding of this mucopolysaccharide correspondingly affected the growth of the yeasts. The results suggest that there are notable differences--at least with respect to the receptors for the F. vesiculosus mucopolysaccharide--between C. guilliermondii, C. krusei and the other Candida species.

Agglutination↗

Enantiomeric separation of drugs by mucopolysaccharide-mediated electrokinetic chromatography.

Chondroitin sulfate C (sodium salt) and heparin (sodium salt), which are both mucopolysaccharides and natural components, have been employed as chiral selectors in electrokinetic chromatography (EKC) for the separation of enantiomers of drugs. These additives are charged, linear, sulfated polysaccharides having large mass. Ionic and hydrophobic interactions are probably the bases for the separation. Among tested drugs that are electrically neutral or basic, trimetoquinol, diltiazem, and their related compounds were successfully enantioseparated by EKC with mucopolysaccharides, especially with chondroitin sulfate C. The choices of pH and the concentration of mucopolysaccharides were found to be important for improvement of enantioselectivity. The acidic buffer solutions were effective for enantioseparation of the solutes in the chondroitin sulfate C system, although no migration of the basic drugs was observed in the heparin system. The results were compared with the enantiomeric separation by EKC with dextran sulfate (sodium salt). The method using chondroitin sulfate C was successfully applied to the optical purity testing of the drug substances.

Chromatography↗

Local responses in primary and secondary human lung cancers. I. Patterns of cellular (eosinophils and macrophages) and extracellular (acid mucopolysaccharide) reactions.

Local free cell (eosinophils and macrophages) and extracellular (acid mucopolysaccharides) reactions were studied by histochemical techniques in 72 primary lung cancers (Group A), 17 pulmonary metastases and 5 lung tumours of unknown origin (Group B). Strong cellular reactions were more frequent in Group A than in Group B, whereas extracellular reactions were more frequent in Group B than in Group A. In both groups the degrees of eosinophilic infiltration and accumulation of acid mucopolysaccharides tended to be negatively correlated. In contrast, macrophages and eosinophils showed a positive correlation in the primary cancers, but none in the other tumours. The extracellular material had physical and chemical properties (solubility, affinity to stains and degradability by enzymes) of the sulphated acid mucopolysaccharides. From its distribution it appeared to be derived from fibroblasts and/or tumour cells.

Eosinophils↗

Binding properties of human thrombospondin: interaction with mucopolysaccharides.

The interaction of human thrombospondin with mucopolysaccharides has been measured quantitatively. Binding of thrombospondin to heparin was examined utilizing an assay employing an 125I-labeled LMW heparin glycosaminoglycan (Mr = 8500). By this means, a class of binding sites was detected that bound approximately 2 moles of LMW heparin per mole of thrombospondin with a Kd of 2.4 nM. The binding stoichiometry of LMW heparin to thrombospondin was confirmed by fluorescence polarization experiments in which thrombospondin bound 3 moles of fluorescamine-labeled LMW-heparin mole protein. A variety of mucopolysaccharides were able to inhibit the interaction of thrombospondin with 125I-LMW heparin, the most effective being heparin sulfate and dermatan sulfate. However, PF4 was found to be an even more potent inhibitor, approximating unfractionated heparin in this respect. The ability of mucopolysaccharides to interact with purified thrombospondin suggests a role for such molecules in the regulation of the biologic activity of thrombospondin, possibly in interactions with connective tissue, such as the subendothelium. Given that there are three binding sites per molecule and that thrombospondin appears to form polymeric aggregates with itself, significant binding energies could be developed.

Animals↗

Mucopolysaccharides produced in tissue culture.

1. A method of mass tissue culture has been devised by which, in a relatively short period of time, samples large enough for chemical isolation of mucopolysaccharides can be obtained. 2. Chemical isolation of acid mucopolysaccharides from mass cultures of human fetal skin, human fetal bone, bovine fetal skin, and rat subcutaneous tissue has been carried out. It has been found that the fibroblasts of each of these tissues produce in tissue culture more than one mucopolysaccharide, namely, hyaluronic acid, and a chondroitin sulfate. 3. The chondroitin sulfate produced by fibroblasts of the above tissues in tissue culture was not fully sulfated. The possible significance of this finding is discussed.

Animals↗

The isolation and characterization of glycopeptides and mucopolysaccharides from plasma membranes of an ascites hepatoma, AH 130.

Plasma membranes were isolated from an ascites hepatoma, AH 130, by the fluorescein mercuric acetate (FMA) method. Glycopeptides and mucopolysaccharides were prepared by digesting the membranes with pronase, then by fractionating the digest chromatographically and electrophoretically. Isolated fractions were analyzed for their amino acid and carbohydrate compositions. Results were compared with those for corresponding fractions from AH 66 (J. Biochem. 76, 319-333 (1974)). Mucopolysaccharides and a series of glycopeptides were isolated from the fraction excluded from Sephadex G-50. The mucopolysaccharides were identified as a family of heparan sulfates with different electrophoretic mobilities. The glycopeptides contained serine, threonine, galactose, galactosamine, glucosamine, and sialic acid as the major constituents as aspartic acid and mannose as minor ones. This suggests that most of the carbohydrate moieties are linked to serine or threonine (O-glycosidic), and that some are linked to asparagine (N-glycosidic). No nearly purely O-glycosidic glycopeptides were found in this fraction from AH 130, through they were the major glycopeptides from the AH 66 plasma membranes. In the fraction included in the gel, glycopeptides containing fucose, galactose, mannose, glucosamine, glaactosamine, and sialic acid were found. The presence of galactosamine suggests that some of the glycopeptides are O-glycosidic though most are N-glycosidic. In the corresponding fraction from AH 66, nearly purely N-glycosidic glycopeptides were found.

Animals↗

Atypical leukodystrophy with accumulations of sulfatide and mucopolysaccharide.

1. Follow-up studies of two siblings with mental retardation, progressive paraplegia and dementia were reported. 2. The brain and visceral organs of a patient (elder brother) who died recently were investigated histopathologically, electronmicroscopically and neurochemically. a. Moderate, diffuse demyelination occurred throughout the white matter of the central nervous system. b. Two abnormal materials were deposited in the white matter: one showed metachromasia containing sulfatide and another had staining characteristics of acid mucopolysaccharide histochemically. Electronmicroscopically, the former was a conglomerate of electron-dense materials of various degrees and the latter had a membrane-limited granular structure. The myocardium contained the same mucopolysaccharide material as that in the brain. c. Slight increase of sulfatide was found in the cerebral white matter. Arylsulfatase A activities were preserved in the brain as well as in the liver. Contents of hexosamine and uronic acid in the white matter were about three or five times as much as that of the controls. Electrophoresis on cellulose acetate membrane showed that acid glucopeptide was the main component of the mucopolysaccharide extracted from the brain.

Adult↗

Behaviour in mucopolysaccharide disorders.

This paper reports a study of the nature and prevalence of behaviour problems in 258 children with mucopolysaccharide disorders. Questionnaire data obtained through the post was supplemented by home visits to 42 families in the sample and by regular discussions with families at meetings of the Society for Mucopolysaccharide Diseases. High rates of behaviour problems were found, particularly in children with Sanfilippo's and Hunter's disease aged 5 to 9 years. These included destructiveness, restlessness, and aggressiveness. Sleep problems were common across subtypes with an overall prevalence of 66%. Parents reported that they received little or no support in the management of these difficult behaviours. It is concluded that behaviour problems are a primary feature of the mucopolysaccharide disorders and place a major strain on families. Services to help families cope with these problems are urgently needed.

Aggression↗