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Biomedical subjects

M D Haust

Publications and source records attributed to M D Haust.

At least 37 records · Page 2Linked to original sources
PubMed1986

Ultrastructural and biochemical aspects of the Sanfilippo syndrome,--type III genetic mucopolysaccharidosis.

The Sanfilippo Syndrome (SS) is a recessively inherited connective tissue disorder expressed in early life. It is classified as a genetic mucopolysaccharidosis (MPS) because the underlying defect involves the catabolism of heparan sulfate (HS), one of the glycosaminoglycans (GAG). Four variant forms, i.e., type A, B, C, and D, each associated with a different enzymatic defect, have been recognized in affected children. Biochemical studies show that characteristically HS accounts for most of the increased amounts of GAG excreted in the urine and those stored in viscera and brain. Gangliosides GM2, GM3 and GD2 are elevated considerably in the brain. Morphologically, the very water-soluble substances accumulating in the viscera are metachromatic, and consist ultrastructurally of finely granulo-floccular (or filamentous) material which is bound in cytoplasmic vacuoles. These substances are considered to represent the GAG. In the central nervous system (CNS) the stored substances are not soluble in water or alcohol and xylol, give a PAS-positive reaction, and stain for lipids and with luxol fast blue. Ultrastructurally, they consist of membranous arrays which often are of the "zebra body" variety. The CNS-inclusions are considered to represent the stored gangliosides; they were found also in small numbers in viscera of older children with SS. The search for a common denominator in the pathogenetic mechanism(s) culminating in both types of inclusions, continues.

Brain↗
PubMed1986

Interstitial collagens in fibrous atherosclerotic lesions of human aorta.

The present study was undertaken to clarify the existing controversy on the collagenous content and composition of human fibrous atherosclerotic versus normal aortic tissues. Several analytic procedures (slab gel electrophoresis; cyanogen bromide peptide mapping; high performance liquid chromatography; ion exchange chromatography) revealed that the amount of the interstitial collagens, i.e. types I and III, was similar in fibrous atherosclerotic lesions and control tissues (70% and 30% respectively). Moreover, when fibrous lesions were analyzed as serial fractions there was a uniform distribution of type I and type III throughout the lesion. Small increases in type III were observed only beneath the lesion where it interfaced with the normal media. The results suggest that contrary to some previous studies no major shifts in the ratio of the interstitial collagens are evident in atherosclerotic lesions as compared to normal intima-media preparations.

Aged↗
PubMed1986

Analysis of the intermediate and basement membrane collagens in fibrous atherosclerotic lesions of human aorta.

The collagens of fibrous atherosclerotic lesions of human aortae obtained at post mortem examination were compared with those of normal intima-media preparations. Assessed quantitatively, pepsin-solubilized types IV, V and VI collagens decreased in relation to types I and III in preparations from lesions as compared to values for controls. The type V collagen in both tissues were composed of alpha 1 (V) and alpha 2 (V) chains in a 2:1 ratio. A novel ("V") collagen polypeptide identical in size to the alpha 1 (V) chain was identified in association with the interstitial collagen fraction in both tissue types. This chain had unique solubility characteristics and cyanogen bromide peptide composition. The exact relation of this polypeptide to the other collagens is not known, but it is possible that it accounts for the reported fluctuations in type V chains in aortic tissues.

Aorta↗
PubMed1985

Glycoproteins on the surface of smooth muscle cells involved in their interaction with type V collagen.

Type V collagen is a major component of the pericellular coat of smooth cells (SMC). The purpose of the present study was to assess biochemically the nature of an in vitro interaction between bovine aortic SMC and type V collagen from the same source. This interaction was originally shown to be mediated by a cell-surface glycoconjugate. Data obtained in the present study suggests that the binding system consists of integral membrane glycoproteins which act alone or in combination with a surface glycolipid in type V attachment. The nature of this system was indicated by the finding of 80 000 and 50 000 components in the plasma membrane fractions which were specifically retained by type V collagen--Sepharose columns and incorporated both methionine and mannose label. Moreover, inhibition of protein synthesis lowered SMC attachment by 25%. The mannose label associated with these components was probably in the form of a simple oligosaccharide at the attachment site since it bound to concanavalin A (ConA) and was sensitive to endoglycosidase H. Iodinated ConA labelling indicated elevated levels of these components were associated with SMC--type V collagen interaction. The attachment region on the type V molecule was localized within the cyanogen bromide peptide 6 of the alpha 2 (V) chain.

Animals↗
PubMed1984

Characterization of basement membrane collagens of bovine aortae.

Collagenous components were extracted from bovine aorta by pepsin digestion. Differential salt precipitations separated the interstitial from the basement membrane (BM) collagens, and the latter were subsequently separated into three distinct types. Ion exchange chromatography, SDS-slab gel electrophoresis, cyanogen bromide and protease V8 peptide mapping, and amino acid analysis were used to characterize the component chains within each of these types. The major BM-class contained three distinct chains which were identical to the alpha 1(V), alpha 2(V) and alpha 3(V) chains of type V collagen from normal human placenta. The stoichiometry of the chains suggests a [alpha 1(V)]2 alpha 2(V)-helical organization, but the role of the alpha 3(V) chain in the overall structural organization of collagen V remains unknown. The second BM-class contained a heterogeneous group of molecules ranging in size from 40 000 to 140 000 daltons. Two predominant chains within this group were characterized as the alpha 1(IV) and alpha 2(IV) chains of type IV collagen. The last class of BM collagens consisted primarily of high molecular weight components; upon reduction these gave rise to two low molecular weight collagenous species (40 K and 45 K) characteristic of type VI, low molecular weight or 'linker' collagens. The functional roles of the isolated BM collagens, either individually or collectively, has not been ascertained to date.

Animals↗
PubMed1984

Ciliated smooth muscle cells in aortic atherosclerotic lesions of rabbit.

Single rudimentary cilia were observed by electron microscopy in smooth muscle cells (SMCs) of aortic fatty streaks in hypercholesterolemic rabbits, but not in aortae of controls. Similar cilia are known to occur in several tissues and various species, but it is believed that they have not so far been identified in the SMCs of atherosclerotic lesions. These cilia differ structurally from the classical type characterising ciliated epithelium. It is currently thought that a sudden transformation from mitotic replicative to nonmitotic structuring tissue may be correlated with the disappearance of centrioles and formation of cilia. The possible implications of the above concept in the overall process of atherosclerosis in the context of our present-day knowledge is briefly discussed.

Animals↗
PubMed1984

Hemodynamic modification of aortic atherosclerosis. Effects of propranolol vs hydralazine in hypertensive hyperlipidemic rabbits.

According to hemodynamic theories of atherogenesis, atherosclerotic plaques are a reaction to endothelial damage caused by arterial flow disturbances such as turbulence. Earlier studies showed that hydralazine increased, whereas propranolol decreased, the product of heart rate X blood velocity, a predictor of arterial flow disturbances, and that hydralazine aggravated, whereas propranolol decreased turbulence in the region of carotid artery stenosis. This study was done to test the hypothesis that drugs which reduce arterial flow disturbances may be more effective in preventing atherosclerosis, than antihypertensive drugs which worsen arterial flow disturbances. Eighty-three New Zealand white rabbits were made hypertensive by a one-kidney Goldblatt procedure, and were fed a 1% cholesterol diet. Untreated hypertensive (P less than 0.01) and hydralazine-treated hypertensive rabbits (P less than 0.05) had significantly more atherosclerosis than did the normotensive controls; propranolol-treated rabbits did not differ significantly from the normotensive controls. Analysis of covariance showed that propranolol-treated rabbits had significantly less atherosclerosis than hydralazine-treated rabbits with blood pressure (P less than 0.04) or heart rate (P less than 0.006) as the covariates.

Animals↗
PubMed1984

Proteoglycans in human atherosclerotic lesions--a pilot qualitative and quantitative study by ruthenium red.

A pilot study was carried out to test whether normal human aorta and aortic atherosclerotic lesions obtained at post-mortem examination were suitable for the demonstration of proteoglycans (PGs) by ruthenium red (RR) staining, and whether by this method qualitative and quantitative differences of PGs might be detectable in various types of lesions and between lesions and the normal aortic intima. The results indicate that the PGs of the above tissues obtained at post mortem were clearly visualized by electron microscopy using the RR-indicator and were thus suitable for quantitative and qualitative evaluation. Of the RR-positive granules only those 20 nm and larger were assessed. RR-granules measuring 20-50 nm were present in normal intima and media, in increased concentration in the innermost part of the mixed fatty-gelatinous lesion, and in a decreased concentration in the fibrous cap of an atherosclerotic plaque. The same RR-granules were observed in a fatty streak and in addition 50-100 nm granules were present in this type of lesion; the overall RR-granule-concentration was reduced here. Granules of both sizes were interconnected by filamentous network. The differential presence of the large (and hitherto unreported) as well as the smaller granules in the various lesions is briefly discussed in the light of the present-day knowledge of tissue-PGs, and the importance of an examination in situ of the compound PGs-complexes in their native form, is emphasized.

Aorta↗
PubMed1982

Ultrastructure of myocardium in the Hurler syndrome. Possible relation to cardiac function.

Cardiac tissues obtained at post mortem examination of eight patients with the Hurler syndrome, who ranged in age from 5 to 23 years, were examined by histochemical methods and electron microscopy. Extensive myocardiocytic vacuolization and increased interstitial fibrous tissue were noted by light microscopy in all hearts. The cytoplasmic (perinuclear) vacuoles contained Luxol-fast-blue-positive substance. At the ultrastructural level, abnormal cytoplasmic organelles were present within the myocardiocytes in all patients. These organelles were of three types: zebra bodies (ZB), membranous cytoplasmic bodies (MCB) and granulomembranous bodies (GMB). As ZB and MCB are believed to represent the morphological counterpart of accumulated gangliosides, these substances rather than glycosaminoglycans appear to be stored within myocardiocytes of patients with the Hurler syndrome. The accumulation of gangliosides and the consequent damage to the myocardial substratum probably contributes to the clinically evident cardiac disease, so often observed in the patients with this disorder.

Adolescent↗
PubMed1981

Ultrastructure of hepatic mitochondria in a child with hyperornithinemia, hyperammonemia, and homocitrullinuria.

Ultrastructural studies of hepatic tissue obtained at biopsy from a nine year old severely retarded boy with hyperornithinemia, hyperammonemia, and homocitrullinuria showed mitochondria of bizarre shapes and unusual internal features. Among the latter were tubules extending throughout the length of the large mitochondria that on cross section had a rosette-like arrangement; the presence of a periodic, approximately 300 A thick, sievelike membrane interposed between the tubules and the inner mitochondrial membrane; and "bulges" of mitochondrial matrix occasionally formed between these two membranes. Since to be metabolized ornithine must enter the mitochondria, the hyperornithinemia is regarded as a reflection of its inability to reach the mitochondrial interior. It is speculated that among other possible causes, the unusual sievelike membrane may be the barrier to ornithine's access to the mitochondrion.

Amino Acid Metabolism, Inborn Errors↗