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Biomedical subjects

J Mossman

Publications and source records attributed to J Mossman.

32 records · Page 2Linked to original sources
PubMed1989

Glomerular and urinary heparan sulphate in congenital nephrotic syndrome.

Studies using cationic probes have suggested that a reduction in glomerular anionic sites, composed principally of the glycosaminoglycan heparan sulphate, is responsible for the abnormal glomerular permeability in the congenital nephrotic syndrome (CNS). We therefore analysed the glycosaminoglycan content of the glomerular basement membrane (GBM) from an infant who died of CNS and from an infant who died of unrelated causes. We also measured the urinary excretion of glycosaminoglycans in children with nephrotic syndrome, both congenital and acquired, and in healthy children. Heparan sulphate constituted 59% of the glycosaminoglycan content of the GBM in the normal infant, the other principal glycosaminoglycan being chondroitin sulphate. In the GBM from the infant with CNS the heparan sulphate was greatly reduced, constituting only 3% of total glycosaminoglycans. The urinary excretion of heparan sulphate was significantly increased in CNS (expressed both in relation to creatinine and to chondroitin sulphate) compared with normal children and to those with acquired nephrotic syndrome. Diminished GBM content of heparan sulphate may be responsible for the abnormal glomerular permeability in CNS and may be a consequence of defective incorporation of heparan sulphate into the GBM with subsequent loss into the urine.

Basement Membrane↗
PubMed1988

Clinical findings in 12 patients with MPS IV A (Morquio's disease). Further evidence for heterogeneity. Part I: Clinical and biochemical findings.

Clinical heterogeneity in MPS IV A (Mucopolysaccharidosis IV A, Morquio Disease Type A)has become more clearly identified in recent years. The clinical findings in 12 cases of MPS IV A are described. Clinical presentation was variable, and some cases were only mildly affected. All showed deficiency of N-acetylgalactosamine-6-sulphate sulphatase in fibroblasts, but the patient with the mildest clinical presentation showed a high residual enzyme activity. The urinary glycosaminoglycans (GAGs) were examined on all patients by a two-dimensional electrophoresis technique which proved to be highly reliable and efficient. In particular, no false negative results were obtained, a problem often encountered with routine screening methods. These cases support the division of MPS IV A into three subgroups: the severe "classical" type, an intermediate type and a mild type, all caused by N-acetylgalactosamine-6-sulphate sulphatase deficiency. Residual enzyme activity may be an important prognostic indicator.

Adolescent↗
PubMed1987

Neuraminidase deficiency: case report and review of the phenotype.

A 12 year old boy with neuraminidase deficiency (sialidosis, mucolipidosis I) is described. His clinical features included coarse facies, cherry red spot, ataxia, myoclonus, and dysotosis multiplex. The level of neuraminidase activity in cultured fibroblasts was very low and intermediate levels were observed in both parents. The clinical disorders associated with neuraminidase deficiency are reviewed.

Child↗
PubMed1985

Prenatal diagnosis of hereditary tyrosinemia by determination of fumarylacetoacetase in cultured amniotic fluid cells.

Fumarylacetoacetase was assayed in cultured amniotic fluid cells from four pregnancies at risk for hereditary tyrosinemia and in 11 controls. The enzyme activity was normal in three of the pregnancies at risk for tyrosinemia and healthy children were born. In the fourth case the enzyme activity was deficient, indicating an affected fetus. As the pregnancy was very advanced it was continued, and the child has tyrosinemia. One parent in one of the four families is a compound heterozygote for the tyrosinemia gene and the recently reported "pseudodeficiency" gene for fumarylacetoacetase. This has important consequences for prenatal diagnosis in this family.

Adult↗
PubMed1983

Prenatal tests for Sanfilippo disease type B in four pregnancies.

We report the prenatal diagnosis of two fetuses with Sanfilippo disease type B. In both pregnancies there were excessive amounts of heparan sulphate in amniotic fluid and the activity of N-acetyl-alpha-D-glucosaminidase was undetectable in cultured amniotic fluid cells. The predictions were confirmed by enzyme assay of cultured skin fibroblasts from the aborted fetus or the affected infant. The disorder was excluded for two other pregnancies at risk and the predictions are considered to be correct because of the normal progress of the healthy children.

Acetylglucosaminidase↗
PubMed1983

Hunter's disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene.

We describe a 3 year old girl with the typical clinical features of the X linked recessive condition, Hunter's disease. The diagnosis was confirmed by the pattern of urinary excretion of glycosaminoglycans and the absence of iduronate sulphatase activity in her fibroblasts. She also had an apparently balanced reciprocal chromosomal translocation 46XX,t(X:5) with the X breakpoint being between q26 and q27. Pedigree analysis, and the normal iduronate sulphatase activity in the mother's fibroblasts, serum, and hair roots indicate that the affected child represents a new mutation. Since the parents' karyotypes are normal, it seems that the translocation disrupted the iduronate sulphatase gene itself, thus mapping this to Xq26-27 for the first time. The severe clinical features, not expected in a girl, may be explained by non-random X inactivation.

Child, Preschool↗
PubMed1982

Prenatal diagnosis of mucopolysaccharidosis by two-dimensional electrophoresis of amniotic fluid glycosaminoglycans.

Amniotic fluid from 72 pregnancies at risk for mucopolysaccharidosis have been analysed for glycosaminoglycans (GAG) by means of two-dimensional electrophoresis. Definite results were obtained in all cases and required only 3 days to report. Of the 66 cases for which GAG analysis was accompanied by enzyme assays on cultured amniotic fluid cells, there was agreement of results in 65. In the one case of disagreement the result of GAG analysis proved to be correct. Fourteen pregnancies were predicted to be affected and the predictions were confirmed by studies on fetal tissues and/or cultured cells, or in one case the birth of an affected infant. Of the 58 pregnancies predicted to be unaffected, 48 have so far gone to term and produced healthy infants. There have been no false negative predictions. The analytical method is simple, rapid, and, in this study, has been found completely reliable to prenatal diagnosis.

Amniotic Fluid↗
PubMed1982

Prenatal diagnosis of a heterozygote for mucopolysaccharidosis type VII (beta-glucuronidase deficiency).

We had the opportunity of investigating a case (BK) of a severe form of mucopolysaccharidosis with nearly total deficiency of beta-glucuronidase in serum, leucocytes and fibroblasts. We here report results obtained by prenatal diagnosis of a clinically normal child (BK's sister), and point out the difficulty in interpreting a heterozygous level of beta-glucuronidase activity in cultured amniotic cells. Four successive passages of amniotic cells were tested for beta-glucuronidase and alpha-mannosidase activity in at-risk and control cells. In different passages, enzyme activity was between 8 and 49 per cent of controls but 2 to 18 times higher than fibroblasts from the affected brother (BK). The highest activity was observed in the first passage and the lowest in the third. The electrophoretic separation of GAGS from at-risk amniotic fluid showed a normal pattern. We discuss the correlation between enzyme levels in different passages of cultured cells and that found in leucocytes and fibroblasts from the propositus and parents. From a practical point of view, we conclude that the first passage gives the most reliable results for prenatal diagnosis.

Adult↗
PubMed1981

Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation.

A one-year-old boy with type I H mucopolysaccharidosis (Hurler's disease) was given a bone-marrow transplant (BMT) from his mother in an attempt to replace the deficient enzyme, alpha-L-iduronidase (iduronidase). These is definite evidence of engraftment, the enzyme activity of the recipient's leucocytes reaching heterozygote levels within 37 days of the BMT. Graft-versus-host disease (GVHD) developed but was partially controlled by steroids. From 3-4 months after graft until the present (13 months after the graft) iduronidase activity has been present in the serum and the urine and there has been evidence of considerable degradation of glycosaminoglycans excreted in the urine. The hepatosplenomegaly has disappeared, corneal clouding has cleared, and deterioration in the child's development seems to have been arrested.

Aminoacridines↗
PubMed1981

Correct prenatal diagnosis of a Hurler fetus where amniotic fluid cell cultures were of maternal origin.

Contamination of amniotic fluid cell cultures by maternal cells can be expected to lead to misdiagnosis of fetal genotype in 0.1 to 0.5/100 cultures, when assays are carried out directly on cultured cells. Chemical analysis of the cell-free amniotic fluid supernatant may overcome this source of error and has the added advantages of speed and independence from amniotic cell culture failure. We describe a pregnancy at risk for Hurler's disease where amniotic cells cultured at amniocentesis had a female karyotype and an alpha-iduronidase activity towards both phenyl and 4-methylumbelliferyl substrates at the lower end of the normal range, suggesting a heterozygous fetus. An affected fetus was predicted, however, because of a high concentration of dermatan sulphate in the amniotic fluid. The discrepancy between these findings was shown to be due to maternal cell contamination of amniotic fluid cell cultures by the birth of a male infant with Hurler's disease.

Amniotic Fluid↗
PubMedDate not supplied

'Dividing the desolation': clients views on the benefits of a cancer counselling service.

This paper describes clients' accounts of the benefits they derived from a short course of cancer counselling provided within a humanist framework. Three hundred and two clients who had attended at least one session of a short course of cancer counselling received an evaluation form, which incorporated both fixed-choice and open-ended questions. One hundred and forty two (47%) clients returned evaluation forms; those who had attended more sessions were significantly more likely to do so. Quantitative data were analysed using SPSS (Statistical Package for the Social Sciences) for Windows and qualitative data using a thematic approach. Almost all clients indicated that they felt they had benefited from counselling. Analysis of the open-ended questions identified nine main benefits of counselling and four key avenues or processes through which clients derived these benefits. Overall, counselling was seen as helping them to work through powerful thoughts and feelings and so to come to terms with cancer and to regain a sense of control in their lives. The benefits of a short course of counselling which clients identified reflect the aims of humanistic counselling which are not well captured by psychiatric assessments or most standard research instruments. In evaluating cancer counselling services, assessments which include these client-defined outcomes may provide a more sensitive way of gauging the value of counselling to a non-clinic population.

Adult↗