PubMed Health⌕ Search

Biomedical subjects

M Z Jones

Publications and source records attributed to M Z Jones.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of goat lysosomal beta-mannosidase using monoclonal and polyclonal antibodies.

Goat beta-mannosidase was purified 120,000-fold in 26% yield from kidney using concanavalin A-Sepharose chromatography followed by immunoaffinity and cation-exchange chromatography. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by Coomassie Blue staining, the purified enzyme preparation consists of 90- and 100-kDa peptides. Both these peptides react with anti-beta-mannosidase monoclonal antibodies and produce similar electrophoretic peptide patterns when subjected to limited proteolysis. Deglycosylation reduces the size of the 90- and 100-kDa peptides to 86 and 91 kDa, respectively. Goat kidney tissues lacking beta-mannosidase activity, acquired from animals affected with beta-mannosidosis, do not contain detectable quantities of the 90- and 100-kDa peptides as judged by monoclonal antibody reactivity. We postulate that the 90- and 100-kDa peptides represent two related forms of beta-mannosidase.

Animals↗
PubMed1992

Determination of sequence and linkage of tissue oligosaccharides in caprine beta-mannosidosis by fast atom bombardment, collisionally activated dissociation tandem mass spectrometry.

Fast atom bombardment, collisionally activated dissociation tandem mass spectrometry (FAB-CAD-MS/MS), combined with p-aminobenzoic acid ethyl ester (ABEE) derivatization, were used to confirm the sequence and linkage pattern of subnanomolar amounts of the previously characterized three major thyroid gland oligosaccharides accumulated in caprine beta-mannosidosis. Positive ion FAB-CAD-MS/MS of both the [M + H]+ and [M + Na]+ ions from the ABEE derivatized oligosaccharides produced product ions derived from cleavage of the glycosidic bonds which allowed the sequences to be determined. Several fragments resulting from cleavages across the sugar ring permitted the assignment, in some cases, of the linkage positions between the sugar residues. The natriated molecule yielded several fragments of this type which were not observed when the protonated molecule was selected as the precursor ion. Use of these techniques gave the complete sequence and linkage characterization of the disaccharide and complete sequence and partial linkage information for the two higher oligosaccharides.

Animals↗
PubMed1992

N-acetylglucosamine 6-sulphatase deficiency in a Nubian goat: a model of Sanfilippo syndrome type D (mucopolysaccharidosis IIID).

A male Nubian goat (SD-1) presented at birth with neurological manifestations consistent with a lysosomal storage disease. Histological studies of tissue obtained at autopsy suggested glycosaminoglycan storage. Total urinary glycosaminoglycan levels, as measured by the uronic acid method, were elevated but overlapped with levels in a younger control goat. However, N-sulphate content was increased 2- to 5-fold, suggestive of heparan sulphate excretion, and this elevation was confirmed by cellulose acetate electrophoresis. Further, urinary levels of free N-acetylglucosamine 6-sulphate were increased 6-fold over controls, SD-1 cultured skin fibroblasts, labelled with [35S]sulphate from the incorporated twice as much radioactivity into macromolecular material as did normal fibroblasts. Forty-eight hours after removal of [35S]sulphate from the medium the SD-1 fibroblasts retained 58% of the label, whereas in control fibroblasts it had declined to 20%, indicative of [35S]proteoglycan storage in SD-1. The assay of fibroblast extracts revealed a profound deficiency of N-acetylglucosamine 6-sulphatase whereas eight other activities including beta-mannosidase, arylsulphatase B, iduronate 2-sulphatase, N-acetylgalactosamine 6-sulphatase, and heparin sulphamidase were normal. Mixing of SD-1 sonicates with normal sonicates showed no evidence of an inhibitor, and mixing of SD-1 sonicates with Sanfilippo D cell sonicates yielded no activity. These data ruled out multiple sulphatase deficiency and suggested the first example of the human Sanfilippo syndrome, type D (N-acetylglucosamine 6-sulphatase deficiency) in goats.

Acetylglucosamine↗
PubMed1992

Oligosaccharides accumulated in the bovine beta-mannosidosis kidney.

The phenotype of bovine beta-mannosidosis (beta-mannosidase deficiency), recently identified in Salers cattle, is similar to the caprine form of the disease (Abbitt et al., 1991). This investigation was designed to characterize accumulated kidney oligosaccharides in bovine beta-mannosidosis. Oligosaccharides were extracted from the kidney of an affected Salers calf and purified by chromatographic techniques. The amount of accumulating oligosaccharides in 1 g of wet tissue was about 21 mumol. Structures of derivatized oligosaccharides were characterized by high-performance liquid chromatography, mass spectrometry, methylation analysis and sequential exoglycosidase digestions. The major accumulating oligosaccharides were Man beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4GlcNAc. Oligosaccharides accumulating in minor amounts were Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc, Man alpha 1-6Man beta 1-4GlcNAc beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc beta 1-4GlcNAc. As in caprine beta-mannosidosis, oligosaccharides with terminal beta-mannose residues and cleaved as well as uncleaved chitobiose linkages were identified in bovine beta-mannosidosis kidney. The accumulating oligosaccharides in tissue were thus identical in bovine and caprine beta-mannosidosis; however, the source of the novel oligosaccharides remains to be determined.

Animals↗
PubMed1992

Bovine plasma beta-mannosidase activity and its potential use for beta-mannosidosis carrier detection.

Plasma beta-mannosidase activities were determined for Salers cattle from 8 herds as an evaluation of this method for detection of beta-mannosidosis heterozygotes. Several biological factors, such as age, gender, herd, and risk of being a beta-mannosidosis carrier, were considered in this study. The mean enzyme activity for obligate heterozygotes (n = 8) was 55 U/ml (range = 43-65 U/ml), which was 59% of the mean enzyme activity for cattle that were low risk for being a carrier. These data indicate that bovine beta-mannosidosis is characterized by a gene dosage effect. The analytical and biological variation of plasma beta-mannosidase activity that was observed necessitates limiting the test to adult fullblood/purebred Salers cattle within a herd. Plasma beta-mannosidase analysis provides important information for intraherd selection of Salers cattle that are heterozygous for beta-mannosidosis.

Aging↗
PubMed1991

Beta-mannosidosis in twelve Salers calves.

A diagnosis of beta-mannosidosis, a lysosomal storage disease caused by a deficiency of beta-mannosidase, was made in 12 purebred Salers calves. Affected neonatal calves were unable to rise and had intention tremors, hidebound skin, slightly domed calvaria, slight prognathism, and narrow palpebral fissures. Postmortem findings included variable dilatation of the lateral cerebral ventricles, marked pallor and paucity of white matter of the cerebrum and cerebellum, and mild to marked bilateral renomegaly. Microscopic lesions consisted of clear, intracytoplasmic vacuoles, which were especially prominent in neurons, thyroid follicular cells, proximal renal tubular epithelium, and reticuloendothelial cells. By ultrastructural examination, the intracytoplasmic vacuoles were identified as membrane-bound lysosomes distended by lucent material. The serum of affected calves was profoundly deficient in beta-mannosidase. Oligosaccharides, principally a trisaccharide with a terminal hexose in the beta-anomeric configuration, accumulated in tissues of affected calves. The percentage (37.2) of affected calves from groups of siblings, the approximately equal sex ratio, and the phenotypic normalcy of the parents of affected calves are compatible with an autosomal recessive mode of inheritance typical of other glycoproteinoses.

Animals↗
PubMed1991

Neuropathology of bovine beta-mannosidosis.

beta-Mannosidosis, an inherited defect of glycoprotein catabolism previously identified in goats and humans, has been recently diagnosed in Salers cattle. This disorder is associated with deficiency of lysosomal beta-mannosidase and accumulation of oligosaccharides. Analysis of bovine beta-mannosidosis neuropathology was initiated to determine whether independently arising gene defects in cattle and goats result in expression of similar lesions. Brain, spinal cord, and selected peripheral nerves from seven affected newborn Salers calves and three normal newborn calves were available for gross, light microscopic, and electron microscopic analysis. Gross examination revealed hydrocephalus of variable severity and myelin deficiency in the cerebral hemispheres, cerebellum, and brainstem. Microscopic examination revealed cytoplasmic vacuolation, myelin deficiency, and axonal spheroids of similar type and distribution to that reported in affected goats. Cytoplasmic vacuolation resulting from lysosomal storage showed consistent variation among cell types. Myelin deficits were more severe in the cerebral hemispheres and cerebellum than in the spinal cord. Axonal spheroids occurred in the cerebrum, brainstem, cerebellum, and trigeminal nerve endings. The presence of similar lesions in bovine and caprine beta-mannosidosis supports a direct relationship with the gene defect.

Animals↗
PubMed1990

Regional central nervous system oligosaccharide storage in caprine beta-mannosidosis.

Goats affected with beta-mannosidosis, an autosomal recessive disease of glycoprotein metabolism, have deficient activity of the lysosomal enzyme beta-mannosidase along with tissue storage of oligosaccharides, including a trisaccharide [Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc] and a disaccharide [Man(beta 1-4)GlcNAc]. CNS myelin deficiency, with regional variation in severity, is a major pathological characteristic of affected goats. This study was designed to investigate regional CNS differences in oligosaccharide accumulation to assess the extent of correlation between oligosaccharide accumulation and severity of myelin deficits. The concentrations of accumulated disaccharide and trisaccharide and the activity of beta-mannosidase were determined in cerebral hemisphere gray and white matter and in spinal cord from three affected and two control neonatal goats. In affected goats, the content of trisaccharide and disaccharide in spinal cord (moderate myelin deficiency) was similar to or greater than that in cerebral hemispheres (severe myelin deficiency). Thus, greater oligosaccharide accumulation was not associated with more severe myelin deficiency. Regional beta-mannosidase activity levels in control goats were consistent with the affected goat oligosaccharide accumulation pattern. The similarity of trisaccharide and disaccharide content in cerebral hemisphere gray and white matter suggested that lysosomal storage vacuoles, more numerous in gray matter, may not be the only location of stored CNS oligosaccharides.

Animals↗
PubMed1990

Giant axonal neuropathy: clinical, electrophysiologic, and neuropathologic features in two siblings.

Giant axonal neuropathy is a progressive central-peripheral axonopathy characterized by distention of axons by aggregated neurofilaments. We report two female siblings with giant axonal neuropathy. Both patients developed symptoms of a chronic progressive polyneuropathy at age 3 years. Clinical evidence of central nervous system involvement was present in both cases. Autopsy neuropathologic examination of the older sibling at the age of 11 years revealed numerous giant axons, Rosenthal fibers, and gliosis throughout the brain and spinal cord and typical giant axons in the peripheral nerves. Electrophysiologic studies in the younger sibling indicated brain stem dysfunction, and her sural nerve biopsy revealed enlarged axons packed with neurofilaments. These patients illustrate that neurologic deficits of giant axonal neuropathy result from widespread lesions in the central, as well as peripheral (including autonomic), nervous systems. This occurrence of giant axonal neuropathy in two siblings supports a genetic origin of this disease. This is the first report of autopsy findings in giant axonal neuropathy in an affected sibling.

Axons↗
PubMed1990

Caprine beta-mannosidosis. Abnormal thyroid structure and function in a lysosomal storage disease.

Deficient activity of the lysosomal enzyme beta-mannosidase leads to widespread tissue accumulation of oligosaccharides in caprine beta-mannosidosis, an autosomal recessive neurovisceral storage disease. Severe thyroid morphologic abnormalities found in a previous light microscopic survey of tissues from neonatal affected goats suggested the possibility of impairment of function. Since considerable evidence indicates that thyroid hormone plays an important role in regulation of myelination, thyroid hormone deficiency, if present during central nervous system development, could be a factor in the hypomyelination seen in affected animals. Thus, this study was designed to characterize thyroid structure and function in beta-mannosidosis. To investigate developmental aspects of structural abnormalities, thyroids from six pairs of affected and control animals ranging in age from 96/150 days gestation to 3 days postnatal were analyzed by light and electron microscopy. Major findings in thyroids from affected animals, as early as 96/150 days gestation, included follicle irregularities and pronounced presence of lysosomal storage vacuoles in all cell types, particularly in follicular cells. The degree of cytoplasmic vacuolation increased with advancing age. To assess thyroid function, thyroid hormone concentrations were determined in six age-matched, neonatal pairs of affected and control goats. Significantly decreased thyroid hormone concentrations were present in affected animals. It is hypothesized that thyroid hormone deficiency plays a role in the pathogenesis of hypomyelination in affected animals. This study comprises, to our knowledge, both the most complete description of developmental abnormalities and the first report of abnormal function in an endocrine organ in a lysosomal storage disease. Further, this report suggests that systemic perturbations induced by a genetically determined deficiency of a lysosomal hydrolase could be a factor in the pathogenesis of central nervous system lesions.

Aging↗
PubMed1988

Partial purification of goat kidney beta-mannosidase.

1. Goat kidney beta-mannosidase was purified 8500-fold to a specific activity of 65,000 nmol/h per mg of protein with a 6% yield by using multiple steps including cation-exchange and anion-exchange fast protein liquid chromatography. This is the first description of a highly purified preparation from goat tissue; however, it was not homogeneous, as judged by silver-stained SDS/polyacrylamide-gel electrophoresis. 2. The enzyme exhibited microheterogeneity when analysed by isoelectric focusing (pI 5.5-6.5). 3. Purified beta-mannosidase hydrolysed the terminal beta-(1----4)-linkage of oligosaccharides that accumulate in beta-mannosidosis.

Animals↗
PubMed1988

Otic pathology of caprine beta-mannosidosis.

Caprine beta-mannosidosis is an autosomal recessive defect of glycoprotein catabolism with a deficiency of tissue and plasma beta-mannosidase activity and tissue accumulation of oligosaccharides within lysosomes. This rapidly fatal genetic disorder of Nubian goats is expressed at birth by a variety of clinical signs including deafness. Affected goats had folded pinnas, and the tympanic cavity was decreased due to multiple, polypoid projections of bone covered by middle ear mucosa which obstructed the view of the cochlear promontory. Numerous cells of the cochlear duct including mesothelial and epithelial cells of Reissner's membrane, mesothelial cells lining the scala tympani, cells of the stria vascularis, numerous supportive cells of the organ of Corti, cochlear hair cells, endothelial cells, perithelial cells, fibroblasts, macrophages, and neurons of the spiral ganglion contained numerous nonstaining intracytoplasmic vacuoles which resulted in distention of affected cells and caused thickening of involved structures. Ultrastructurally, the vacuoles were membrane-bound and consistent with lysosomes. Vacuolated cells were desquamated into the scala vestibuli and scala tympani. This is one of few reports describing light and electron microscopic otic alterations of a storage disease. Goats with beta-mannosidosis appear to be good models of hearing loss in patients with storage disease.

Animals↗
PubMed1986

Caprine beta-mannosidosis: phenotypic features.

The clinical features of caprine beta-mannosidosis were evaluated in 10 newborn goats, one stillborn goat and one goat fetus. The phenotypic abnormalities observed in all 10 live affected animals included an inability to rise from a recumbent position, moderate to marked intention tremor, eye movements resembling pendular nystagmus, clinical deafness, bilateral Horner's syndrome, carpal contractures, pastern joint hyperextension, thickened skin and to a varying degree, a dome-shaped skull. Subjective evaluation suggested that most animals had a decreased muscle mass. Together, these characteristics represent a common phenotype which is expressed at birth in caprine beta-mannosidosis.

Animals↗
PubMed1986

Glycoprotein metabolism in normal and beta-mannosidase-deficient cultured goat skin fibroblasts.

Cultured skin fibroblasts established from goats affected with beta-mannosidosis, an inherited neurovisceral storage disorder, showed an absence of lysosomal beta-mannosidase activity and the corresponding accumulation of a trisaccharide (TS) with the structure Man beta (1----4)GlcNAc beta (1----4)GlcNAc (0.4 mumol/g) and lesser amounts (0.15 mumol/g) of a Man beta (1----4)GlcNAc disaccharide (DS). By using purified storage TS isolated from fibroblasts metabolically labelled with [3H]GlcN, no conversion of TS into DS could be demonstrated in homogenates of affected cells at either lysosomal pH (4.4) or cytosolic pH (6.1), or in the culture medium (pH 7.0) of affected cells. Both TS and DS were secreted into the culture medium by affected fibroblasts. When affected fibroblasts were treated with tunicamycin before labelling with [3H]GlcN, the accumulation of both labelled TS and DS was completely inhibited. Treatment of both affected and normal goat fibroblasts with swainsonine resulted in the inhibition of lysosomal alpha-mannosidase activity and in the accumulation of the same labelled oligosaccharides in both. The major storage pentasaccharide from both normal and affected swainsonine-treated fibroblasts was sensitive to digestion with alpha-mannosidase and endo-beta-N-acetylhexosaminidase D, suggesting a branched mannose structure and a chitobiose core. In the absence of evidence for the existence of unusual N-linked glycoprotein-associated chitotriose oligosaccharide structures in affected goat fibroblasts, it must be concluded that degradative pathways for N-linked oligosaccharides are similar in both normal and affected goat fibroblasts, and that these pathways differ from catabolic pathways in human fibroblasts.

Alkaloids↗