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Biomedical subjects

M Jay

Publications and source records attributed to M Jay.

At least 91 records · Page 5Linked to original sources
PubMed1992

Localization of two genes for Usher syndrome type I to chromosome 11.

The Usher syndromes (USH) are autosomal recessive diseases characterized by congenital sensorineural hearing loss and progressive pigmentary retinopathy. While relatively rare in the general population, collectively they account for approximately 6% of the congenitally deaf population. Usher syndrome type II (USH2) has been mapped to chromosome 1q (W. J. Kimberling, M. D. Weston, C. Möller, et al., 1990, Genomics 7: 245-249; R. A. Lewis, B. Otterud, D. Stauffer, et al., 1990, Genomics 7: 250-256), and one form of Usher syndrome type I (USH1) has been mapped to chromosome 14q (J. Kaplan, S. Gerber, D. Bonneau, J. Rozet, M. Briord, J. Dufier, A. Munnich, and J. Frezal, 1990. Cytogenet. Cell Genet. 58: 1988). These loci have been excluded as regions of USH genes in our data set, which is composed of 8 French-Acadian USH1 families and 11 British USH1 families. Both of these sets of families show linkage to loci on chromosome 11. Linkage analysis demonstrates locus heterogeneity between these sets of families, with the French-Acadian families showing linkage to D11S419 (Z = 4.20, theta = 0) and the British families showing linkage to D11S527 (Z = 6.03, theta = 0). Genetic heterogeneity of the data set was confirmed using HOMOG and the M test (log likelihood ratio > 10(5)). These results confirm the presence of two distinct USH1 loci on chromosome 11.

Chromosome Mapping↗
PubMed1992

Linkage analysis in X-linked congenital stationary night blindness.

X-linked congenital stationary night blindness (XL-CSNB) is a nonprogressive disorder of the retina, characterized by night blindness, reduced visual acuity, and myopia. Previous studies have localized the CSNB1 locus to the region between OTC and TIMP on the short arm of the X chromosome. We have carried out linkage studies in three XL-CSNB families that could not be classified as either complete or incomplete CSNB on the criteria suggested by Miyake et al. (1986. Arch. Ophthalmol. 104: 1013-1020). We used markers for the DXS538, DMD, OTC, MAOA, DXS426, and TIMP loci. Two-point analyses show that there is close linkage between CSNB and MAOA (theta max = 0.05, Zmax = 3.39), DXS426 (theta max = 0.06, Zmax = 2.42), and TIMP (theta max = 0.07, Zmax = 2.04). Two multiply informative crossovers are consistent with CSNB lying proximal to MAOA and distal to DXS426, respectively. Multipoint analysis supports this localization, giving the most likely order as DMD-17 cM-MAOA-7.5 cM-CSNB-7.5 cM-DXS426/TIMP-cen, and thus refines the localization of CSNB.

Female↗
PubMed1992

Exclusion of chromosome 6 and 8 locations in nonrhodopsin autosomal dominant retinitis pigmentosa families: further locus heterogeneity in adRP.

Genetic studies have revealed that 25 to 30% of autosomal dominant retinitis pigmentosa (adRP) families have mutations in the rhodopsin gene, while the remainder do not. More recently linkage data and mutation detection have demonstrated two further loci implicated in adRP, at an as yet unidentified gene on chromosome 8p and at the human gene homologue of the mouse Rds (Retinal Degeneration Slow) gene on chromosome 6p. We have previously reported exclusion of adRP from the rhodopsin locus on 3q in two large adRP families. We now report exclusion data for both families, on chromosomes 6 and 8, demonstrating that the adRP phenotype results from mutations in at least four locations.

Chromosome Mapping↗
PubMed1992

Noninvasive in vivo percutaneous absorption measurements using X-ray fluorescence.

X-ray fluorescence (XRF) has been used to determine in vivo the percutaneous absorption of 5-iodouracil (5IU) in dimethyl sulfoxide (DMSO) on female Sprague-Dawley rats. An average absorption rate constant of 122 +/- 34 micrograms/cm2-hr was obtained from the XRF measurements on four rats. A comparative study was performed with radiolabeled (125I) 5IU in which the absorption rate constant was determined to be 126 +/- 20 micrograms/cm2-hr. The XRF system described provides a simple, noninvasive means of measuring the percutaneous absorption rate of select compounds by the surface disappearance method.

Animals↗
PubMed1992

Poly(L-lactic acid) microspheres containing neutron-activatable holmium-165: a study of the physical characteristics of microspheres before and after irradiation in a nuclear reactor.

The solvent evaporation technique was employed to prepare poly(L-lactic acid) (PLA) microspheres with 165Ho acetylacetonate (Ho-AcAc). Particle size, percentage Ho-165, percent residual solvent, and retentive ability of the spheres were found to be strongly affected by preparatory conditions. Differential scanning calorimetry (DSC) thermograms suggested that the Ho-AcAc existed in the PLA matrix as a molecular dispersion. High neutron flux irradiations of the PLA spheres in a nuclear reactor produced Ho-166, a therapeutic radionuclide that emits high-energy negatrons (Emax = 1.84 MeV; half-life = 26.9 hr). The gamma radiation dose (53-75 Mrad) from the core of the reactor provided an overkill of all bioburdens in the PLA spheres. Gel permeation chromatography (GPC) analysis showed that these irradiations caused a reduction in PLA molecular weight. Infrared spectra, 13C NMR spectra, 1H NMR spectra, and DSC thermograms further confirmed the presence of lower molecular weight PLA but proved the overall maintenance of PLA structure.

Bacillus↗
PubMed1992

A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa.

Recently it has been demonstrated that some families with autosomal dominant retinitis pigmentosa (adRP) have mutations in the rhodopsin gene while others do not. Previously we have identified six such mutations in seven adRP families in this laboratory, one of which was previously described in US patients. We now present a completed screen of the rhodopsin gene in a panel of 39 adRP families, by a rapid screening technique which will be of use for routine diagnosis. Nine different mutations were ultimately found, in a total of twelve of the 39 families. These include the six previously identified mutations, in codons 68-71, 190, 211, 255, 296 and 347, two new ones in codons 53 and 106, and another mutation first identified in a single US patient, in codon 58. Thus approximately 30% of adRP families have 'Rhodopsin RP' while the remainder probably have a defect elsewhere in the genome. Of those families in which rhodopsin mutations have been found, four have been classified D type, three as sectorial RP and the remainder are of uncertain classification. All families excluded from chromosome 3q by linkage have been classified R type. These data suggest a correlation between clinical sub-classification and the underlying rhodopsin/non-rhodopsin heterogeneity.

Amino Acid Sequence↗
PubMed1992

Nine generations of a family with autosomal dominant retinitis pigmentosa and evidence of variable expressivity from census records.

We present a nine generation family with autosomal dominant retinitis pigmentosa (ADRP). Evidence of blindness in the early generations, as obtained from census returns and clinical records, and examination of current patients show variable expressivity with a spectrum which ranges from asymptomatic in late life to blindness in the third decade of life. The family is not linked to any of the chromosomal locations so far described in ADRP and further illustrates the heterogeneity of the disorder.

Adolescent↗
PubMed1992

Evidence for a pseudoautosomal locus for schizophrenia. I: A replication study using phenotype analysis.

A locus for schizophrenia within the pseudoautosomal region of chromosomes X and Y has been suggested by Crow on the basis of epidemiological data. The present report replicates this finding in a sample of 38 French multiply affected families with schizophrenia. Sibship and pairwise analysis, with or without weighted-pair correction, with three different systems of family classifications, showed there to be an excess of same-sex pairs in paternally derived sibships, as predicted by the pseudoautosomal hypothesis.

Female↗
PubMed1992

Evidence for a pseudoautosomal locus for schizophrenia. II: Replication of a non-random segregation of alleles at the DXYS14 locus.

Because of an association between sexual aneuploidies and schizophrenia, and because schizophrenic siblings have been found to be more often of the same than of the opposite sex, the susceptibility locus for schizophrenia is thought to lie within the pseudoautosomal region of the sex chromosomes. We analysed 33 sibships comprising 18 pairs, 13 trios, and 2 quartets of affected siblings, and found support for non-random segregation of of alleles at the DXYS14 locus in affected siblings. These findings are consistent with the pseudoautosomal hypothesis for schizophrenia and favour a genetic linkage between DXYS14 and the disease.

Alleles↗
PubMed1992

Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families.

Autosomal dominant retinitis pigmentosa (adRP) has shown linkage to the chromosome 3q marker C17 (D3S47) in two large adRP pedigrees known as TCDM1 and adRP3. On the basis of this evidence the rhodopsin gene, which also maps to 3q, was screened for mutations which segregated with the disease in adRP patients, and several have now been identified. However, we report that, as yet, no rhodopsin mutation has been found in the families first linked to C17. Since no highly informative marker system is available in the rhodopsin gene, it has not been possible to measure the genetic distance between rhodopsin and D3S47 accurately. We now present a linkage analysis between D3S47 and the rhodopsin locus (RHO) in five proven rhodopsin-retinitis pigmentosa (rhodopsin-RP) families, using the causative mutations as highly informative polymorphic markers. The distance, between RHO and D3S47, obtained by this analysis is theta = .12, with a lod score of 4.5. This contrast with peak lod scores between D3S47 and adRP of 6.1 at theta = .05 and 16.5 at theta = 0 in families adRP3 and TCDM1, respectively. These data would be consistent with the hypothesis that TCDM1 and ADRP3 represent a second adRP locus on chromosome 3q, closer to D3S47 than is the rhodopsin locus. This result shows that care must be taken when interpreting adRP exclusion data generated with probe C17 and that it is probably not a suitable marker for predictive genetic testing in all chromosome 3q-linked adRP families.

Chromosome Mapping↗
PubMed1992

Polymeric microspheres for radionuclide synovectomy containing neutron-activated holmium-166.

Poly-L-lactic acid (PLA) microspheres containing neutron-activated 166Ho were investigated as potential agents for radionuclide synovectomy. Stable 165Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 microns (range 2-13 microns) containing 25.4% 165Ho-AcAc (9.1% 165Ho) were irradiated in a high neutron flux to produce 31.1-36.0 mCi 166Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 +/- 0.01% of the 166Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257-591 microCi 166Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed 166Ho retention in the joint space after 120 hr of 97.7% +/- 0.8% and 98.2% +/- 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the 166Ho make them attractive agents for radionuclide synovectomy.

Animals↗
PubMed1991

Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site.

Several mutations in the rhodopsin gene in patients affected by autosomal dominant retinitis pigmentosa (ADRP) have recently been described. We report four new rhodopsin mutations in ADRP families, initially identified as hetero-duplexed PCR fragments on hydrolink gels. One is an in-frame 12-bp deletion of codons 68 to 71. The other three are point mutations involving codons 190, 211, and 296. Each alters the amino acid encoded. The codon 190 mutation has been detected in 2 from a panel of 34 ADRP families, while the remaining mutations were seen in single families. This suggests that, consistent with a dominant condition, no single mutation will account for a large fraction of ADRP cases. The base substitution in codon 296 alters the lysine residue that functions as the attachment site for 11-cis-retinal, mutating it to glutamic acid. This mutation occurs in a family with an unusually severe phenotype, resulting in early onset of disease and cataracts in the third or fourth decade of life. This result demonstrates a correlation between the location of the mutation and the severity of phenotype in rhodopsin RP.

Amino Acid Sequence↗
PubMed1991

A historic case of visual agnosia revisited after 40 years.

In one of the seminal works on visual agnosia, Adler (1944, 1950) presented the case of a 22-yr-old woman who sustained carbon monoxide cerebral toxicity in the Cocoanut Grove nightclub diaster of 1942. We located this patient 40 yrs after injury and performed a detailed reevaluation. The patient demonstrated persistent deficits in visual recognition, characterized most prominently by defective recognition of elemental shape and form, associated with alexia, prosopagnosia, visuospatial disorientation and impaired visual imagery. Visual acuity, colour recognition, writing ability and verbal intelligence were relatively preserved. Isolated bilateral occipital injury was demonstrated by CT and MRI scanning. On comparison with previously reported cases, our results support the hypothesis that carbon monoxide toxicity can induce a visual agnosia of the apperceptive type with well defined characteristics, seldom seen with other types of cerebral injury. Prognosis for long-term recovery is poor.

Accidents↗
PubMed1991

Genetic localisation of the RP2 type of X linked retinitis pigmentosa in a large kindred.

Genetic linkage and deletion studies have led to the proposal that there are at least two loci on the X chromosome which are responsible for X linked retinitis pigmentosa (XLRP). One locus (RP3) has been closely defined by genetic linkage and deletion analyses and localised to the region between the ornithine transcarbamylase (OTC) and chronic granulomatous disease (CYBB) loci in Xp21.1-p11.4. The other locus (RP2) has been assigned by linkage analysis alone to region Xp11.4-p11.2, but its localisation is less well defined. The results of a multipoint linkage analysis of a single large XLRP kindred using eight informative loci provide further evidence on the localisation of RP2 to this region. The maximum likelihood location of this locus shows a multipoint lod score of 7.17 close to DXS255 (in Xp11.22) and TIMP (in Xp11.3-p11.23), neither of which show recombination with RP2, in an area extending from 2 cM proximal to DXS7 to 1 cM distal to DXS14 (approximate 95% confidence limits).

Bayes Theorem↗