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Biomedical subjects

M Z Jones

Publications and source records attributed to M Z Jones.

At least 37 records · Page 2Linked to original sources
PubMed1995

Development and efficacy of ultrasound-guided fetal fluid aspiration techniques for prenatal diagnosis of caprine beta-mannosidosis.

Ultrasound-guided fetal fluid sampling was performed on 13 pregnant goats at Days 59 to 65 of gestation to establish safe techniques for accurate sampling and to determine the feasibility of prenatal diagnosis of beta-mannosidosis. Fluids were analyzed for electrolyte and creatinine content to assess accuracy of sampling. Values correlated well with previously reported concentrations for caprine and ovine fetal fluids at the same gestational stage. The single abortion which occurred following ultrasound-guided sampling was correlated with placentome penetration and aspiration of bloody fluids. Thin layer chromatography of amniotic and allantoic fluids was performed to detect oligosaccharides that accumulate in beta-mannosidosis. Abnormal accumulated oligosaccharides were identified in the allantoic but not amniotic fluid from a beta-mannosidase-deficient 62-d-old fetus. Thus, allantocentesis was shown to be an optimal, safe procedure for providing information at this gestational stage to diagnose caprine beta-mannosidosis.

Journal Article↗
PubMed1993

Bovine kidney beta-mannosidase: purification and characterization.

Lysosomal beta-mannosidase was purified 160,000-fold in 24% yield from bovine kidney by a four-step purification procedure, which included concanavalin A-Sepharose, immunoaffinity, TSK-butyl and h.p.l.c. cation-exchange chromatography. When analysed by SDS/PAGE and detected by Coomassie Blue or silver staining, the purified enzyme preparation consists of two prominent peptides (100 and 110 kDa) and a third minor peptide (84 kDa). These three peptides are immunologically related and are consistently associated with beta-mannosidase activity in all chromatographic steps. Removal of N-linked carbohydrate from the 84, 100 and 110 kDa peptides decreases their molecular sizes to 75, 86 and 91 kDa respectively. Bovine kidneys lacking beta-mannosidase, activity, acquired from calves affected with beta-mannosidosis, do not contain detectable quantities of the three beta-mannosidase peptides, as judged by monoclonal- and polyclonal-antibody reactivity.

Animals↗
PubMed1993

Possible beta-mannosidosis chimera. Altered expression of metabolic perturbations.

An aberrant beta-mannosidosis phenotype in a 5-month-old triplet goat kid was characterized by a late postnatal onset of mild neurological symptoms. Necropsy examination revealed relatively normal myelination; however, the distribution of cytoplasmic vacuolation in the kidney and brain was similar to that observed in neonatal beta-mannosidosis. Variable engraftment of donor stem cells, resulting from transplacental transfusion of stem cells from a normal sibling during the immunotolerant period, may have modified the expected severe beta-mannosidosis phenotype. This investigation was designed to determine the effects of a possible chimeric state on organ-specific metabolic perturbations. Residual beta-mannosidase enzyme activity was found in plasma, kidney, liver and spleen but not in brain. Other lysosomal enzyme activities were comparable to normal values. Immunoreactive beta-mannosidase was estimated to be less than 10% of normal levels. Kidney, brain grey matter and brain white matter contained 33%, 12% and 4%, respectively, of the oligosaccharides expected in the organs of beta-mannosidosis animals. There were no detectable oligosaccharides or cytoplasmic vacuolation in the liver or spleen. Studies of this possible chimera provided preliminary evidence for the efficacy of prenatal treatment of early-onset neurodegenerative disorders.

Animals↗
PubMed1993

Pathologists' participation in postmortem examinations for patients with dementia.

Pathologists (n = 571) in Michigan were surveyed to examine the problem of limited access to autopsy experienced by families of patients with dementia and to assist with the implementation of the Michigan Dementia Program. The survey determined the extent to which pathologists performed autopsies for patients with dementia and/or were willing to do so as part of a statewide Postmortem Examination Program. Responses from 394 pathologists (69%) indicated that 49% were willing to perform brain removal and 44% were interested in learning more about the statewide program. The survey results were used to recruit pathologists, to identify potential problems, and to provide baseline data against which to measure the effects of a fully implemented program.

Attitude of Health Personnel↗
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↗