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P J Wilson

Publications and source records attributed to P J Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Genetic mapping on the mouse X chromosome of human cDNA clones for the fragile X and Hunter syndromes.

Murine X-linked genes corresponding to the human Fragile X (FMR1) and Hunter syndrome (IDS) loci have been mapped in an interspecific backcross between B6CBA-Aw-J/A-Bpa and Mus spretus using human cDNA clones. Pedigree analysis of recombinants from a total of 248 backcross progeny favors a gene order of (Cf-9, Mcf-2)-(Fmr-1)-Ids-Gabra3-Rsvp. Gene order is conserved between the species, although no fragile site has been detected in the mouse in this region of the murine X chromosome.

Animals↗
PubMed1992

Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.

Hunter syndrome or mucopolysaccharidoses type II (MPS-II), is a lysosomal storage disorder caused by a deficiency in the activity of the enzyme iduronate-2-sulphatase (IDS). We have investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS-II patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations of the IDS gene were found in DNA from 9 patients two of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoint of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constitute major rearrangements of the gene. Interestingly, six of these rearrangements showed similar or identical patterns by Southern analysis suggestive for a region prone to structural alterations within the IDS gene. We also demonstrate the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. A contiguous gene deletion syndrome characterized by Hunter syndrome and epilepsy is also discussed.

Blotting, Southern↗
PubMed1992

Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.

We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of the Xq27.3-q28 loci: DXS297 (VK23AC), DXS293 (VK16), FRAXA (pfxa3), DXS296 (VK21A), and the 3' end of the iduronatesulfatase (IDS) gene. The flanking loci--DXS52 (St14-1), DXS304 (U6.2), and DXS369 (RN1)--were intact. On the basis of these results, we concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Both Southern analysis of DNA from somatic cell hybrids, using short segments of IDS cDNA, and PCR of reverse-transcribed RNA from cultured skin fibroblasts indicated that the telomeric terminus of the deletion was localized to a region near the middle of the coding sequences of the gene.

Autoradiography↗
PubMed1991

Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.

Hunter syndrome is a human X-linked disorder caused by deficiency of the lysosomal exohydrolase iduronate-2-sulphatase (IDS). The consequent accumulation of the mucopolysaccharides dermatan sulphate and heparan sulphate, in the brain and other tissues, often results in death before adulthood. There is, however, a broad spectrum of severity that has been attributed to different mutations of the Hunter syndrome gene. We have used an IDS cDNA clone to localise the IDS gene to Xq28, distal to the fragile X mutation (FRAXA). One-third of Hunter syndrome patients had various deletions or rearrangements of their IDS gene, proving that different mutations are common in this condition. Deletions of the IDS gene can include a conserved locus that is tightly linked to FRAXA, suggesting that deletion of nearby genes may contribute to the variable clinical severity noted in Hunter syndrome. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation.

Blotting, Southern↗
PubMed1991

The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).

Two patients with a complete deletion of the iduronate-2-sulphatase (IDS) gene are described. In both patients, the resulting phenotype was that of very severe Hunter syndrome (mucopolysaccharidosis II). In addition, both had features not commonly seen in this disorder, e.g. early onset of seizures in one patient and ptosis in the other. It is speculated that loss of adjacent loci may contribute to the unusual findings and that the severe features present in both patients may represent contiguous gene syndromes. Further analysis of IDS cDNA from other patients with Hunter's syndrome may eventually enable phenotype to be predicted more accurately.

Blotting, Southern↗
PubMed1991

Genetic mapping of new RFLPs at Xq27-q28.

The development of the human gene map in the region of the fragile X mutation (FRAXA) at Xq27 has been hampered by a lack of closely linked polymorphic loci. The polymorphic loci DXS369 (detected by probe RN1), DXS296 (VK21A, VK21C), and DXS304 (U6.2) have recently been mapped to within 5 cM of FRAXA. The order of loci near FRAXA has been defined on the basis of physical mapping studies as cen-F9-DXS105-DXS98-DXS369-DXS297-FRAXA-++ +DXS296-IDS-DXS304-DXS52-qter. The probe VK23B detected HindIII and XmnI restriction fragment length polymorphisms (RFLPs) at DXS297 with heterozygote frequencies of 0.34 and 0.49, respectively. An IDS cDNA probe, pc2S15, detected StuI and TaqI RFLPs at IDS with heterozygote frequencies of 0.50 and 0.08, respectively. Multipoint linkage analysis of these polymorphic loci in normal pedigrees indicated that the locus order was F9-(DXS105, DXS98)-(DXS369, DXS297)-(DXS293,IDS)-DXS304-DXS52. The recombination fractions between adjacent loci were F9-(0.058)-DXS105-(0.039)-DXS98-(0.123)-DXS369-(0.00)- DXS297-(0.057)-DXS296- (0.00)-IDS-(0.012)-DXS304-(0.120)-DXS52. This genetic map will provide the basis for further linkage studies of both the fragile X syndrome and other disorders mapped to Xq27-q28.

Female↗
PubMed1990

Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA.

Iduronate 2-sulfatase (IDS, EC 3.1.6.13) is required for the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations causing IDS deficiency in humans result in the lysosomal storage of these glycosaminoglycans and Hunter syndrome, an X chromosome-linked disease. We have isolated and sequenced a 2.3-kilobase cDNA clone coding for the entire sequence of human IDS. Analysis of the deduced 550-amino acid IDS precursor sequence indicates that IDS has a 25-amino acid amino-terminal signal sequence, followed by 8 amino acids that are removed from the proprotein. An internal proteolytic cleavage occurs to produce the mature IDS present in human liver shown to contain a 42-kDa polypeptide N-terminal to a 14-kDa polypeptide. The IDS sequence has strong sequence homology with other sulfatases (such as sea urchin arylsulfatase, human arylsulfatases A, B, and C, and human glucosamine 6-sulfatase), suggesting that the sulfatases comprise an evolutionarily related family of genes that arose by gene duplication and divergent evolution. The arylsulfatases have a greater homology with each other than with the non-arylsulfatases (IDS and glucosamine 6-sulfatase). The IDS cDNA detected RNA species of 5.7, 5.4, 2.1, and 1.4 kilobases in human placental RNA and revealed structural alterations and gross deletions of the IDS gene in many of the clinically severe Hunter syndrome patients studied.

Amino Acid Sequence↗
PubMed1989

HLA class II DR, DQ, and DP restriction fragment length polymorphisms in rheumatoid arthritis.

HLA class II restriction fragment length polymorphisms (RFLPs) were studied in 43 individuals with established seropositive rheumatoid arthritis (RA) and in a group of healthy controls. All patients and controls were tissue typed for HLA-A, B, and DR antigens. Rapid, initial screening for RA associated RFLPs was conducted by pooling DNA samples from 11 HLA-DR4 positive patients with RA and comparing the RFLP patterns with those seen in a pool of DNA samples drawn from 11 HLA-DR4 positive healthy controls. Candidate RA associated RFLPs were examined in our full panel of patients with RA and controls. In most cases the RFLPs detected showed no significant association with RA. An exception was a 13.0 kb DraI DQ beta associated RFLP, which, when HLA-DR4 positive patients with RA and controls were considered alone, showed a weak positive association with susceptibility to RA. This RFLP was not associated with known DR, DQ, or Dw specificities. These results show a distinct paucity of class II RA associated RFLPs but may indicate a role for DQ beta genetic variation in the aetiology of RA.

Arthritis, Rheumatoid↗
PubMed1989

A comparison of serological, cellular and DNA-RFLP methods for HLA matching in the selection of related bone marrow donors.

Serological, cellular and DNA-RFLP (restriction fragment length polymorphism) methods of determining HLA compatibility between 10 leukaemic patients and potential related bone marrow donors were systematically compared. DR beta/DQ alpha/DQ beta/DNA-RFLP typing of these families gave results in agreement with those obtained by serological methods (matching for HLA-A, -B and -DR), supported by mixed lymphocyte culture (MLC) data, indicating the validity and accuracy of DNA-RFLP matching in transplantation. However, a significant minority of four leukaemic patients plus two healthy individuals were not clearly HLA-DR typable by serology, but all such individuals were easily typable by DNA-RFLP. These results were supported by MLC data, where available. In addition, all data were in agreement with previously reported correlations between DNA-RFLPs and HLA-DR serology, allowing unambiguous assignment of HLA-DR types where these were previously in doubt. These results demonstrate the value of DNA-RFLP HLA class II DR and DQ typing in leukaemic patients requiring marrow transplantation who are not clearly typable by traditional methods and suggest that this approach should constitute an important element of future HLA matching programmes for bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1988

Detection of kidney reactive antibodies at crossmatch in renal transplant recipients.

We have investigated retrospectively sera from 70 renal allograft recipients for the presence of antibodies binding to a preanastomosis biopsy of the donor kidney by an indirect immunoperoxidase technique. All recipients had a negative T cell lymphocytotoxic crossmatch. A positive immunoperoxidase crossmatch for kidney-reactive antibodies was seen in 13/70 (18.6%) recipients--6 reacting with endothelium, 4 with epithelium, and 3 with both cell types. Neither the presence of these antibodies nor their pattern of staining correlated with recipient graft outcome. Following transplantation endothelial reactive antibodies developed in 15/43 (35%) patients, whereas tubular epithelial antibodies occurred in 5/43 (12%). The antibodies were persistent and accompanied graft failure in 10/14 (71%) patients, while transient antibodies were only associated with graft failure in 2/12 (17%) recipients. Development of lymphocytotoxic antibodies did not correlate with the presence of renal reactive antibodies or eventual graft outcome. Smooth muscle and antinuclear antibodies in recipient sera prior to transplantation were associated with improved graft survival. Eluates of 8/14 rejected grafts confirmed the presence of renal reactive antibodies, with patterns of staining similar to those observed in recipient sera. Antibodies in 7/8 recipients were shown by absorption studies to have HLA class I and/or II specificity, the remaining recipient having proximal tubular brush border antibodies.

Adolescent↗
PubMed1988

Ultraviolet microbeam irradiation of chromosomal spindle fibres shears microtubules and permits study of the new free ends in vivo.

Irradiation of birefringent chromosomal spindle fibres in crane-fly spermatocytes in metaphase I or anaphase I produces an area of reduced birefringence (ARB) on the fibre. This ARB moves poleward and is lost at the pole. Ultrastructural and immunofluorescence analysis of ARBs obtained by irradiation with monochromatic ultraviolet light of wavelength 260 nm shows that the microtubules in the irradiated area are depolymerized, though the rest of the spindle appears unaffected. The area of microtubule depolymerization moves poleward with the ARB, and once the ARB reaches the pole the irradiated half-spindle appears normal. The motion of the ARB, therefore, appears to be due to the behaviour of the sheared microtubules in the chromosomal spindle fibre. The relative stability of the sheared microtubules shows that chromosomal fibre microtubules are not dynamically unstable, as are microtubules under certain conditions in vitro. However, ARB motion may be due to a moderated version of dynamic instability. Possible models for ARB motion are discussed.

Animals↗
PubMed1988

Misleading clinical syndromes of CSF shunt malfunction.

CSF shunt malfunction is nowadays a common emergency. It may occasionally simulate some more sinister underlying central nervous system disease. We describe three examples where simple mechanical revision of a faulty shunt reversed bizarre and misleading neurological syndromes.

Adult↗
PubMed1986

Diabetes and schizophrenia--a preliminary study.

The results of a small scale retrospective study are presented. The study was initiated to determine the incidence of diabetes in long-stay patients in two psychiatric hospitals in Northern Ireland and to attempt to define whether there was a relationship between the two disease states, schizophrenia and diabetes mellitus. There was a higher percentage of diabetics in the two institutions than was expected. It was concluded that drug therapy of the mental illness may have had a contributory effect on the subsequent development of diabetes mellitus.

Antipsychotic Agents↗
PubMed1979

Functional budgeting.

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Attitude of Health Personnel↗
PubMed1975

Meningioma after contralateral hemispherectomy for malignant glioma: case report.

A patient is described who successfully underwent cerebral hemispherectomy for malignant glioma and whose death nine months later, wrongly ascribed to recurrent malignancy, was in fact due to a subsequently-developing benign meningioma in the remaining hemisphere. The possible advantages of a modification of standard hemispherectomy technique are also discussed.

Adult↗