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Biomedical subjects

M Jay

Publications and source records attributed to M Jay.

At least 37 records · Page 2Linked to original sources
PubMed1998

Anticipation in schizophrenia: no evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases.

A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Adult↗
PubMed1998

Solubility enhancement of phenol and phenol derivatives in perfluorooctyl bromide.

Perfluorinated solvents are gaining popularity as pulmonary ventilation fluids, but they suffer from poor solvent quality in concurrent drug delivery applications. The present study examines the use of a hydrophobic solubilizing agent capable of interacting with model drug solutes by hydrogen bonding with the purpose of enhancing solubility in perfluorooctyl bromide (PFOB). A series of solubilizing agents containing a ketone carbonyl to act as a hydrogen bond acceptor and a perfluoroalkyl chain to maintain the solubility of the putative complex in PFOB are investigated. The solubility of phenol in PFOB is enhanced to the greatest extent by 1-(4-perfluorobutyl phenyl)-1-hexanone (III) where the ketone carbonyl is protected from the electron withdrawing effects of the perfluorobutyl chain by a phenyl ring. Experiments with solubilizers lacking the ketone group suggest that pi-pi bond interactions of III with phenol do not significantly enhance solubility. For a series of phenol derivatives, a rank-order correlation exists between the magnitude of solubility enhancement by III, as reflected by the calculated association constants, and the Hammett sigma parameter of the phenols. Because the O-methyl-substituted phenols do not have the ability to hydrogen bond, their solubility is not enhanced by the presence of III. The results of the present study indicate that solubility of model drug hydrogen bond donating compounds can be enhanced in PFOB by the presence of fluorocarbon-soluble hydrogen bond acceptors.

Chromatography, High Pressure Liquid↗
PubMed1997

Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21.

Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by retinitis pigmentosa, polydactyly, obesity, hypogenitalism, mental retardation, and renal anomalies. To detect linkage to BBS loci, 29 BBS families, of mixed but predominantly European ethnic origin, were typed with 37 microsatellite markers on chromosomes 2, 3, 11, 15, 16, and 17. The results show that an estimated 36-56% of the families are linked to the 11q13 chromosomal site (BBS1) previously described by M. Leppert et al. (1994, Nature Genet. 7, 108-112), with the gene order cen-D11S480-5 cM-BBS1-3 cM-D11S913/D11S987-qter. A further 32-35% of the families are linked to the BBS4 locus, reported by R. Carmi et al. (1995, Hum. Mol. Genet. 4, 9-13) in chromosomal region 15q22.3-q23, with the gene order cen-D15S125-5 cM-BBS4-2 cM-D15S131/D15S204-qter. Three consanguineous BBS families are homozygous for three adjacent chromosome 15 markers, consistent with identity by descent for this region. In one of these families haplotype analysis supports a localization for BBS4 between D15S131 and D15S114, a distance of about 2 cM. Weak evidence of linkage to the 16q21 (BBS2) region reported by A. E. Kwitek-Black et al. (1993, Nature Genet. 5, 392-396) was observed in 24-27% of families with the gene order cen-D16S408-2 cM-BBS2-5 cM-D16S400. A fourth group of families, estimated at 8%, are unlinked to all three of the above loci, showing that at least one other BBS locus remains to be found. No evidence of linkage was found to markers on chromosome 3, corresponding to the BBS3 locus, reported by V. C. Sheffield et al. (1994, Hum. Mol. Genet. 3, 1331-1335), or on chromosome 2 or 17, arguing against the involvement of a BBS locus in a patient with a t(2;17) translocation.

Abnormalities, Multiple↗
PubMed1997

Further epidemiological evidence for anticipation in schizophrenia.

Anticipation describes an inheritance pattern within a pedigree in which disease severity increases, and/or age at onset decreases, in successive generations. This phenomenon has been described in different samples of schizophrenic subjects, and could explain many inconsistencies in the inheritability of schizophrenia. Anticipation is, however, subject to numerous and significant biases, partially controlled by different methodologies used in different studies. We analyzed the anticipation effect on an original sample of schizophrenic patients (n = 57) who had at least one other schizophrenic in their family belonging to another generation (father/mother, uncle/aunt, son/daughter). We tested the anticipation effect according to previously published methodologies, such as percentages of parent-child pairs showing negative versus positive anticipation, comparison of anticipation limited to parent-child or uncle-nephew pairs, anticipation analysis on the basis of families with unilineal origins only, and comparison of the age at onset-survival distribution of the two generations. The 31 schizophrenic subjects who belonged to the younger generation had a significantly earlier age at onset (24.58 years) than the 26 schizophrenic subjects who belonged to the older generation (36.46 years). Whatever the method used to control biases, we significantly found earlier age at onset for schizophrenic patients from the younger generation. There is strong evidence for the existence of the anticipation effect in schizophrenia in our sample, as well as in various others, which may elucidate numerous inconsistencies in clinical and epidemiological data which characterize schizophrenia. Looking for expanded trinucleotide repeats is thus the next step to detect the gene(s) that are potentially involved.

Adult↗
PubMed1997

Purification of proteins using foam fractionation.

Purification is an important step in the production of pharmaceuticals from recombinant proteins. The characteristics of industrial-scale purification schemes, such as conventional chromatography, have a significant impact on the cost of production. Foam fractionation, a novel separation technique based upon the differences in affinities of components for the gas/aqueous interface of a foam, has the potential to be a cost-effective component in a purification scheme. This review covers some of the more recent studies in understanding the process and applications of foam fractionation in protein-containing systems with special attention to the requirements of pharmaceutical products.

Chromatography, Gas↗
PubMed1997

Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp.

PURPOSE: Proximal Xp harbors many inherited retinal disorders, including retinitis pigmentosa (RP) and congenital stationary night blindness, both of which display genetic heterogeneity. X-linked congenital stationary night blindness (CSNBX) is a nonprogressive disease causing night blindness and reduced visual acuity. Distinct genetic loci have been reported for CSNBX at Xp21.1, which is potentially allelic with the RP3 gene, and at Xp11.23, which is potentially allelic with the RP2 gene. The study to identify the RP2 gene led to an extended study of families with potentially allelic diseases that include CSNBX. METHODS: Haplotype analysis of a family diagnosed with CSNBX was performed with 17 polymorphic markers on proximal Xp covering previously identified loci for CSNBX and XLRP. Two-point and multipoint lod scores were calculated. RESULTS: Informative recombinations in this family define a locus for CSNBX (CSNB4) with flanking markers DXS556 and DXS8080 on Xp11.4 to Xp11.3, an interval spanning approximately 5 to 6 cM. A maximum lod score of 3.2 was calculated for the locus order DXS556-1 cM-(CSNB4-DXS993)-2 cM-DXS1201. CONCLUSIONS: The results describe a new localization for CSNBX (CSNB4) between the RP2 and RP3 loci on proximal Xp. CSNB4 is not allelic with any previously reported XLRP loci; however, the interval overlaps the locus reported to contain the cone dystrophy (COD1) gene, and both diseases are nonrecombinant with DXS993. Because mutations in the RPGR gene to date account for disease in only a small proportion of RP3 families, the possibility that this new locus (CSNB4) also segregates with an as yet unidentified XLRP locus cannot be excluded.

Chromosome Mapping↗
PubMed1996

No season-of-birth effect in schizophrenic patients from a tropical island in the Southern Hemisphere.

The distribution of birth rates was examined in 668 schizophrenic patients born in Réunion, a tropical French island in the Southern Hemisphere, and compared with that in the general local population. We failed to observe a significant season-of-birth effect, either in the total sample of schizophrenic patients or in subgroups categorized by gender, age, or family history of schizophrenia. Seasonal factors do not appear to affect the yearly distribution of births among schizophrenic patients on Réunion Island. It is nevertheless possible that environmental factors which are seasonal in countries with more contrasting climates have a continuous effect, throughout the whole year, in subtropical areas. Conversely, these findings provide some evidence against the hypothesis that there is an age-incidence artifact in seasonal studies from countries in the Northern Hemisphere.

Adult↗
PubMed1996

Doyne revisited.

Inherited retinal dystrophies are important causes of blindness in the Western world. Molecular genetic techniques, and the use of large pedigrees exhibiting such conditions, have been instrumental in finding causative disease genes. The genealogy of families with a rare condition known as Doyne's honeycomb retinal degeneration was first described in 1899. Investigating this phenotype is extremely important because of the similarities it shares with age-related macular degeneration, and it may lead us to a gene that is involved in this complex genetic trait. In this paper we review the original genealogy of the families described by Doyne, and explain the methods used to identify the living descendants of these families.

Choroiditis↗
PubMed1996

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Amino Acid Sequence↗
PubMed1996

Occupational exposure leading to hantavirus pulmonary syndrome in a utility company employee.

Hantavirus pulmonary syndrome is a newly recognized rodent-borne zoonosis. We report a case of hantavirus pulmonary syndrome in an employee of a California utility company who was probably occupationally exposed to Sin Nombre virus. Environmental assessment and genetic comparison of the patient's hantavirus isolates to hantavirus isolates from rodents trapped at possible sites of exposure suggested that the patient contracted his infection at the work site. The study revealed a close correspondence between the patient's viral genotype and that from a rodent trapped at the work site. This report alerts the public health and medical community to the fact that employees of utility companies and similar industries may be an important risk group in areas where hantavirus is endemic and emphasizes the need to incorporate strategies for preventing exposure to hantavirus and other emerging infections into occupational safety protocols.

Animals↗
PubMed1996

Epidemiologic linkage of rodent and human hantavirus genomic sequences in case investigations of hantavirus pulmonary syndrome.

Sin Nombre virus (SNV) causes the zoonotic disease hantavirus pulmonary syndrome (HPS). Its mechanisms of transmission from rodent to human are poorly understood. It is possible that specific genetic signature sequences could be used to determine the probable site of each case-patient's exposure. Environmental assessments suggested 12 possible sites of rodent exposure for 6 HPS patients. Rodents were captured at 11 of the 12 sites and screened for SNV infection within 2 weeks of the patient's diagnosis. Viral sequences amplified from tissues of rodents at each site were compared with those from case-patients' tissues. Rodents bearing viruses with genetic sequence identity to case-patients' viruses across 2 genomic segments were identified in 4 investigations but never at >1 site. Indoor exposures to rodents were especially common at implicated sites. By distinguishing among multiple possible sites of exposure, viral genotyping studies can enhance understanding of the conditions associated with infection by SNV.

Animals↗
PubMed1996

Retinal dystrophies and genetic counselling.

Increased patient demand is leading to a corresponding increase in the need for informed genetic counselling in ophthalmic practice which requires refined diagnosis, and a detailed knowledge of molecular genetics. Accurate assessment of risk and visual potential in prospective children is becoming available for a range of retinal dystrophies allowing for more educated decisions to be made by parents.

Ethics, Medical↗
PubMed1996

Anticipation in schizophrenia: new light on a controversial problem.

OBJECTIVE: Anticipation, recently found in several neuropsychiatric disorders, is an inheritance pattern within a pedigree in which disease severity increases or age at onset decreases in successive generations. Demonstration of genetic anticipation in schizophrenia could be of heuristic value, since unstable trinucleotide repeat DNA is known to be the biological basis of anticipation. However, to overcome one of the major ascertainment biases that might mimic anticipation--namely, the fact that patients in different generations are not interviewed at the same age, resulting in a greater chance of finding a later age at onset in the older generation--a new method of investigating anticipation was used. METHOD: The study subjects were 97 systematically ascertained schizophrenic patients belonging to 24 families with at least two generations affected who were identified during a 1-year prevalence study in a limited geographical area of Reunion Island (Indian Ocean). A method of calculating expected age at onset according to age at interview was used in the analyses. RESULTS: In the younger generation of patients, the observed age at onset (21.80 years) was earlier than the expected age at onset (24.95 years), demonstrating anticipation, even when five additional biases that can mimic this genetic effect--the proband effect, the presence of an affected father or mother, the bilineality of the illness, the fertility effect, and the cohort effect--were taken into account. CONCLUSIONS: Evidence for anticipation was demonstrated in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia.

Adult↗
PubMed1996

Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.

Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (ARP), accounting for approximately 25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This "bimodal expressivity" contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus.

Chromosome Mapping↗
PubMed1995

A trinucleotide deletion together with a base duplication event at codon 439 in the human tyrosinase gene identifies a mutational hotspot.

Molecular analysis of the human tyrosinase gene in two patients suffering from a temperature-sensitive form of albinism has identified a thymine triplet deletion at codon 439 which is accompanied by a duplication of the immediately preceding cytosine residue. This results in a two base pair frame shift leading to premature termination at codon 448, giving a truncated protein. Its relationship to other mutations in tyrosinase and the possible cause are discussed. The temperature-sensitive phenotype is due to the guanine to adenine mutation at codon 422, known to generate a temperature-sensitive enzyme. The CTTT at F439 in tyrosinase is also present at F508 in CFTR, the main mutation causing cystic fibrosis.

Adolescent↗
PubMed1995

Further evidence for anticipation in schizophrenia.

The term 'anticipation' is used to describe the increase in disease severity or the decrease in age of onset in succeeding generations within families. This phenomenon has been related to expansion of trinucleotide repeat DNA sequences in some genetic illnesses. We examined age of onset among two generations in familial schizophrenia. Twenty-six unilineal pedigrees previously ascertained for linkage studies were used. We defined the older generation as G1 and the younger generation as G2. Cumulative survival analysis for intergenerational pairwise comparisons in groups G1 and G2 showed a significantly earlier age of onset in G2 (10 years earlier). Additional analyses, which took into account some biases such as the censoring effect of age at interview and preferential ascertainment of late-onset parents, did not modify the results. No evidence for genomic imprinting was found in our sample. We conclude that anticipation occurs in our sample of familial schizophrenia.

Adolescent↗