Search PubMed⌕ Search

Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 109 records · Page 6Linked to original sources
PubMed1993

Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells.

The GM2 activator is a hexosaminidase A-specific glycolipid-binding protein required for the lysosomal degradation of ganglioside GM2. Genetic deficiency of GM2 activator leads to a neurological disorder, an atypical form of Tay-Sachs disease (GM2 gangliosidosis variant AB). Here, we describe a G506 to C transversion (Arg169 to Pro) in the mRNA of an infantile patient suffering from GM2-gangliosidosis variant AB. Using the polymerase chain reaction amplification and direct-sequencing technique, we found the patient to be homozygous for the mutation, whereas the parents were, as expected, heterozygous. BHK cells transfected with a construct of mutant cDNA gave no GM2 activator protein detectable by the Western blotting technique, whereas those transfected by a wild-type cDNA construct showed a significant level of human GM2 activator protein. The substitution of proline for the normal Arg169 therefore appears to result in premature degradation of the mutant GM2 activator, either during the post-translational processing steps or after reaching the lysosome. The basis for the phenotype of GM2 gangliosidosis variant AB may therefore be either inactivation of the physiological activator function by the point mutation or instability of the mutant protein.

Animals↗
PubMed1993

Whose responsibility is it anyway? Hospital admission and discharge of older people in an inner-London District Health Authority.

The division of responsibilities that exists between primary and secondary health care services and health and social care services may create problems in the provision of care to patients whose needs mean that a number of different agencies are involved in their care. The objective of all the agencies involved is the smooth transfer of clients between different sectors of care provision. One client group thought to be particularly vulnerable to dislocations in the continuous pattern of care provision is older people. Problems over the division of responsibility between professional groups are particularly evident on admission to and discharge from hospital. It is the latter rather than the former aspect that has been the focus of research. An extensive multi-methods study of the admission and discharge of older people from hospital in an inter-city District Health Authority was undertaken. This paper examines the transfer of older people between different elements of the health and social care systems. Our study illustrates that on neither admission nor on discharge was there a clearly defined mechanism for affecting liaison between hospital and community. Clearly, the responsibility for this task must be delegated to a specific group. However, such responsibility must be given within a properly resourced and managed system, otherwise the current position of blurred responsibilities will remain. It is unclear as to how the reform of the National Health Service and the introduction of the internal market and the purchaser/provider division will aid the improved co-ordination which this study has identified as being required.

Aged↗
PubMed1993

Prospective survey of the use of the laryngeal mask airway in 2359 patients.

Patients undergoing anaesthesia in which the laryngeal mask airway was used were prospectively audited over a 6-month period. A simple record sheet was completed at the time of anaesthetic administration and 2359 completed forms were analysed to assess problems encountered with its use. It was used successfully in 2350 patients (99.61%); of these, 1399 patients (59%) breathed spontaneously through the airway and 960 patients (41%) underwent intermittent positive pressure ventilation of the lungs. Two patients (0.08%) were reported to have regurgitated during the use of the laryngeal mask airway, but no serious sequelae associated with its use were encountered.

Adolescent↗
PubMed1993

Clinical improvement after unusual avoidance measures in the home of an atopic dermatitis patient.

A 27-year-old female office clerk with widespread atopic dermatitis (AD) since infancy appeared to be highly sensitized and exposed to molds, storage mites, and chicken feathers and moderately sensitized to house-dust mites and grass and birch pollens. Hardly any textiles were present in her home; that is, only 28 m2, which is less than 25% of the Dutch national average. The causal relationship between eczema and molds plus storage mites in this case of AD was strengthened by the positive effect of an unusual, multidisciplinary home-sanitation program involving cleaning of mineral surfaces and ventilation improvement. This home-sanitation program led to a gradual drop of total IgE and clinical symptom scores to 21% and 13%, respectively, of the original values.

Adult↗
PubMed1993

A 5' splice site mutation in fucosidosis.

Fucosidosis is a rare, autosomal recessive, lysosomal storage disease, resulting from a deficiency of the enzyme alpha-fucosidase (EC 3.2.1.51). It is characterised clinically by progressive mental and motor deterioration, growth retardation, coarse facies, and often recurrent infections, but the course of the disease is variable. The gene encoding lysosomal alpha-fucosidase has been mapped to the short arm of chromosome 1 at position 1p34.1-36.1 and has been called FUCA1. Two mutations causing disease have been described previously, a C-->T change in exon 8 giving rise to a premature, in frame TAA stop codon, and a deletion of at least two exons from the 3' end of the gene. In this paper we present evidence that a homozygous G-->A transition in the first position of the 5' splice site of intron 5 of FUCA1 is the disease causing mutation in a 9 year old child of distantly related parents. A new banding pattern was detected in the patient by Southern blotting of genomic DNA using TaqI restriction and a cDNA FUCA1 probe. The patient was homozygous for this pattern. Three sibs with alpha-fucosidase activity below the normal reference range and both parents were heterozygous. This pattern was not detected in 26 other fucosidosis patients and has not been found in any controls. The mutation was localised by a combination of restriction mapping using different cDNA probes, single stranded conformational polymorphism analysis of exons and flanking regions amplified by the polymerase chain reaction, and by direct sequencing of the amplified sequence. A view of the nature of the mutation, its cosegregation with the disease mutation and its absence in controls, it is probable that the 5' splice site mutation causes fucosidosis in this child.

Base Sequence↗
PubMed1993

Collaborative study of the molecular epidemiology of Tay-Sachs disease in Europe.

Tay-Sachs disease is a lipidosis due to the deficiency of the lysosomal hexosaminidase A. In order to understand the molecular mechanisms of this enzyme deficiency we studied 42 patients of different ethnic origins diagnosed in Europe. The strategy used consists in HEXA cDNA amplification followed by allele-specific oligonucleotide analysis for the frequent mutations, and by chemical cleavage mismatch and denaturing gradient gel electrophoresis for the detection of new mutations. 90% of alleles were clarified in this way, showing a high heterogeneity of HEXA lesions in Tay-Sachs disease. 28 different mutations were found, 20 being identified for the first time in this group of patients.

Adult↗
PubMed1993

Human corneal epithelial primary cultures and cell lines with extended life span: in vitro model for ocular studies.

PURPOSE: To develop an in vitro model of human corneal epithelium that can be propagated in serum-free medium that is tissue specific, species specific, and continuously available. METHODS: Primary explant cultures from human cadaver donor corneas were generated and subsequently infected with Adeno 12-SV40 (Ad12-SV40) hybrid virus or transfected with plasmid RSV-T. RESULTS: Several lines of human corneal epithelial cells with extended life span were developed and characterized. Propagation of both primary cultures and lines with extended life span, upon collagen membranes at an air-liquid interface, promoted multilayering, more closely approximating the morphology observed in situ. CONCLUSIONS: In vitro models, using primary cultures of corneal epithelium and lines of corneal epithelial cells with extended life span, retain a variety of phenotypic characteristics and may be used as an adjunct to ocular toxicology studies and as a tool to investigate corneal epithelial cell biology.

Adenoviruses, Human↗
PubMed1993

Heparin binding proteins. Contribution to heparin rebound after cardiopulmonary bypass.

BACKGROUND: Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, can lead to excessive postoperative bleeding after cardiac surgery. We investigated the mechanism of heparin rebound by using chemically modified heparin that lacks anticoagulant activity (low-affinity heparin) but that is able to displace protein-bound anticoagulantly active heparin. METHODS AND RESULTS: Sixteen patients undergoing elective cardiac surgery were given heparin (400 U/kg) to achieve an activated clotting time (ACT) > 400 seconds. After cardiopulmonary bypass, protamine sulfate was given (by heparin-ACT dose-response curve) to return the ACT to prebypass times (preoperative, 160 +/- 9 seconds; postoperative, 156 +/- 17 seconds). Blood samples were obtained serially for 24 hours and assayed for thrombin clotting time (TCT) and heparin activity using an anti-factor Xa assay. The TCT and anti-factor Xa activity were consistently and abnormally elevated for the first 6 hours after surgery. The anti-factor Xa activity increased fourfold after the addition of low-affinity heparin (essentially free of anti-factor Xa activity), indicating that anticoagulantly active heparin persisted in the circulation after protamine neutralization bound nonspecifically to plasma proteins. Blood loss correlated with postoperative TCTs. CONCLUSIONS: Our findings demonstrate that heparin anticoagulant activity persists for up to 6 hours after surgery despite apparent protamine neutralization. The observation of the marked increase in plasma anti-factor Xa activity after the addition of low-affinity heparin suggests that after its administration, a large proportion of the heparin binds to plasma proteins and is incompletely removed by protamine. After protamine is cleared, the protein-bound heparin dissociates slowly and binds to anti-thrombin III to produce an anticoagulant effect.

Antithrombin III↗
PubMed1992

Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X-inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X-inactivation, and is not specific to the properties of the disease causing gene.

DNA Probes↗
PubMed1992

Administration of human recombinant IL-7 to normal and irradiated mice increases the numbers of lymphocytes and some immature cells of the myeloid lineage.

In vitro experiments performed by several investigators have demonstrated that IL-7 is a growth factor for immature B lymphocytes, thymocytes, and mature T lymphocytes. To evaluate the potential therapeutic use for human rIL-7 (rhuIL-7) as a hematopoietin, we have studied the in vivo hematopoietic effects of rhuIL-7 in mice. In these experiments, sublethally irradiated and normal mice were treated with or without rhuIL-7 for up to 26 days. Administration of rhuIL-7 significantly increased the white blood cell count in the peripheral blood and spleen in both normal and irradiated mice. Treatment with rhuIL-7 also accelerated lymphocytic recovery in irradiated mice. Precursor and mature B lymphocytes showed the greatest expansion in response to rhuIL-7 administration, with smaller increases in T lymphocytes being observed. In mice recovering from high dose irradiation, rhuIL-7 treatment resulted in preferential expansion of CD8+ T lymphocytes and more rapid normalization of the CD4/CD8 ratios. Differential analysis of peripheral blood smears demonstrated that rhuIL-7 also increased the numbers of immature granulocytes in both normal and irradiated mice. Moreover, administration of rhuIL-7 to normal, irradiated, cyclophosphamide-pretreated, or 5-fluorouracil-pretreated mice increased the number of acetylcholinesterase-positive megakaryocytes in the spleen, but not the bone marrow. Therefore, although the major in vivo effects of rhuIL-7 were on cells of the lymphocytic lineage, rhuIL-7 also increased the numbers of some immature cells of the myeloid lineage.

Animals↗
PubMed1992

Heparin binding to plasma proteins, an important mechanism for heparin resistance.

Heparin dosage requirements vary widely among patients with venous thromboembolism. In this study, we measured the proportion of anticoagulantly-active heparin which was reversibly bound and neutralized by plasma proteins (defined as reversible heparin neutralization) in the pre-treatment plasma (in vitro) and in the 6 h post-treatment plasma (ex vivo) of patients with venous thromboembolism treated with a fixed dose of heparin. Reversible heparin neutralization was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. The results indicate that reversible heparin neutralization due to binding to plasma proteins is a major determinant of the anticoagulant response to a fixed dose of standard heparin 6 h post-treatment and of the eventual heparin dose required to achieve a therapeutic anticoagulant effect on days 3-5 of heparin treatment.

Adult↗
PubMed1992

Fetal presentation of Morquio disease type A.

A fetus with mucopolysaccharidosis type IV A (Morquio type A) is described. The family had one affected child exhibiting symptoms of classical Morquio A disease, and late in the subsequent pregnancy prenatal diagnosis was requested. At 23 weeks' gestation, moderate ascites was detected by detailed ultrasound scan and keratan sulphate was found in the amniotic fluid. The pregnancy was terminated by prostaglandin induction and the diagnosis of mucopolysaccharidosis type IV A was confirmed by demonstration of a deficiency of N-acetylgalactosamine-6-sulphate (GalNac-6-S) sulphatase in cultured amniotic cells and in post-mortem fibroblast cultures. The activities of beta-galactosidase and arylsulphatase A were normal, ruling out Morquio disease type B and multiple sulphatase deficiency. These results indicate that mucopolysaccharidosis IV A (a disease that predominantly affects the skeletal system) may produce ascites in the fetus to such an extent that it can be detected by ultrasound.

Amniocentesis↗
PubMed1992

Bone marrow transplantation for Sanfilippo disease type B.

Allogeneic bone marrow transplantation was performed on twins with Sanfilippo B disease. They were the first two patients with this disorder to undergo the procedure. There was definite evidence of engraftment as shown by conversion to donor blood group antigen and tissue type, and increased leukocyte alpha-glucosaminidase activity. Nine years post transplant, neither twin is as handicapped as her untreated brothers were at the same age, although in one twin hyperactivity and behavioural problems, characteristic of the disorder, are present. Details of the twins' intellectual development and growth, their alpha-glucosaminidase activity and urinary glycosaminoglycan excretion are reported.

Bone Marrow Transplantation↗
PubMed1992

Salpingoscopy: systematic use in diagnostic laparoscopy.

OBJECTIVE: To evaluate the importance of salpingoscopy together with laparoscopy in the diagnosis of tubal pathology. DESIGN: Salpingoscopy was performed as a complementary method in patients who were subjected to diagnostic laparoscopy. The relationship between the salpingoscopy and (1) the patient's previous history of tubal disease and (2) laparoscopic diagnoses was evaluated. SETTING: Private patients referred to the Instituto de Fertilidad, Buenos Aires. PATIENTS, PARTICIPANTS: Forty-two patients undergoing a diagnostic laparoscopy during the evaluation of their fertility or as a follow-up of previous therapy. MAIN OUTCOME MEASURE(S): Salpingoscopy was performed, using a colpomicrohysteroscope. We evaluated alterations in major and minor folds and their vascularization, the presence of microadhesions, and cellular nuclei dyed with methylene blue in the tubal lumen. RESULTS: Fifty percent of the patients who had no previous history of tubal disease presented with endosalpingeal alterations, and in 37% of the normal laparoscopies the salpinx had unilateral or bilateral salpingoscopic abnormalities. CONCLUSIONS: Salpingoscopy is a useful method to evaluate oviducts, before assuming their normality, and consideration of these women for assisted reproductive technology.

Abortion, Spontaneous↗
PubMed1992

Care of the dying: an ethical and historical perspective.

OBJECTIVE: To provide a historical perspective, from ancient Greece to the middle of the 20th century, on ethical issues and principles commonly associated with medical care for the dying in Western civilization. SOURCES: Writings of noted philosophers, historians, ethicists, and physicians, as well as published legal and ethical guidelines. INFORMATION EXTRACTION: The sources used highlight the origins of various ethical principles associated with care of the dying. They also identify the opinions of prominent individuals throughout the history of medical ethics. SUMMARY: Devotion to medical beneficence, concern for the quality of life, and respect for the sanctity of life are all expressed in the earliest medical and philosophical writings of ancient Greece. With regard to care of the dying, these considerations led to a wide acceptance of avoiding or terminating treatment in hopeless cases. They also led to active debate regarding medicine's role in hastening the dying process. The rise of Christianity during the Middle Ages markedly suppressed such debate by strongly reinforcing the principle of sanctity of life. Later, the optimism of the enlightenment added the hope of prolonging life. Finally, modern advances in medical science have made that hope a reality of complex ethical dimensions. CONCLUSIONS: Ethical debates regarding appropriate care for the dying are as old as medicine itself. Although beneficent concerns have characterized the medical community in almost every period of history, tensions have repeatedly arisen as diverse religious and philosophical ideologies have produced varying standards to define such beneficence. In the Christian world, the sanctity of life was often extolled as the paramount standard. For the ancient Greeks and Romans, and again in many post-Renaissance philosophies, quality of life considerations assumed equal or greater importance. Modern life-prolonging technologies heighten the debate by allowing these two standards to dramatically conflict, particularly in the critical care setting.

Beneficence↗