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Biomedical subjects

B Salmon

Publications and source records attributed to B Salmon.

At least 19 recordsLinked to original sources
PubMed2003

Linkage analysis of candidate regions using a composite neurocognitive phenotype correlated with schizophrenia.

As schizophrenia is genetically and clinically heterogeneous, systematic investigations are required to determine whether ICD-10 or DSM-IV categorical diagnoses identify a phenotype suitable and sufficient for genetic research, or whether correlated phenotypes incorporating neurocognitive performance and personality traits provide a phenotypic characterisation that accounts better for the underlying variation. We utilised a grade of membership (GoM) model (a mathematical typology developed for studies of complex biological systems) to integrate multiple cognitive and personality measurements into a limited number of composite graded traits (latent pure types) in a sample of 61 nuclear families comprising 80 subjects with ICD-10/DSM-IV schizophrenia or schizophrenia spectrum disorders and 138 nonpsychotic first-degree relatives. GoM probability scores, computed for all subjects, allowed individuals to be partly assigned to more than one pure type. Two distinct and contrasting neurocognitive phenotypes, one familial, associated with paranoid schizophrenia, and one sporadic, associated with nonparanoid schizophrenia, accounted for 74% of the affected subjects. Combining clinical diagnosis with GoM scores to stratify the entire sample into liability classes, and using variance component analysis (SOLAR), in addition to parametric and nonparametric multipoint linkage analysis, we explored candidate regions on chromosomes 6, 10 and 22. The results indicated suggestive linkage for the familial neurocognitive phenotype (multipoint MLS 2.6 under a low-penetrance model and MLS>3.0 under a high-penetrance model) to a 14 cM area on chromosome 6, including the entire HLA region. Results for chromosomes 10 and 22 were negative. The findings suggest that the familial neurocognitive phenotype may be a pleiotropic expression of genes underlying the susceptibility to paranoid schizophrenia. We conclude that use of composite neurocognitive and personality trait measurements as correlated phenotypes supplementing clinical diagnosis can help stratify the liability to schizophrenia across all members of families prior to linkage, allow the search for susceptibility genes to focus selectively on subsets of families at high genetic risk, and augment considerably the power of genetic analysis.

Adolescent↗
PubMed2001

Herpes simplex virus DNA packaging sequences adopt novel structures that are specifically recognized by a component of the cleavage and packaging machinery.

The product of the herpes simplex virus type 1 U(L)28 gene is essential for cleavage of concatemeric viral DNA into genome-length units and packaging of this DNA into viral procapsids. To address the role of U(L)28 in this process, purified U(L)28 protein was assayed for the ability to recognize conserved herpesvirus DNA packaging sequences. We report that DNA fragments containing the pac1 DNA packaging motif can be induced by heat treatment to adopt novel DNA conformations that migrate faster than the corresponding duplex in nondenaturing gels. Surprisingly, these novel DNA structures are high-affinity substrates for U(L)28 protein binding, whereas double-stranded DNA of identical sequence composition is not recognized by U(L)28 protein. We demonstrate that only one strand of the pac1 motif is responsible for the formation of novel DNA structures that are bound tightly and specifically by U(L)28 protein. To determine the relevance of the observed U(L)28 protein-pac1 interaction to the cleavage and packaging process, we have analyzed the binding affinity of U(L)28 protein for pac1 mutants previously shown to be deficient in cleavage and packaging in vivo. Each of the pac1 mutants exhibited a decrease in DNA binding by U(L)28 protein that correlated directly with the reported reduction in cleavage and packaging efficiency, thereby supporting a role for the U(L)28 protein-pac1 interaction in vivo. These data therefore suggest that the formation of novel DNA structures by the pac1 motif confers added specificity on recognition of DNA packaging sequences by the U(L)28-encoded component of the herpesvirus cleavage and packaging machinery.

Base Sequence↗
PubMed2001

Juxtafacet cyst of the lumbar spine. Clinical, radiological and therapeutic aspects in 28 cases.

OBJECT: A consecutive series of 28 "operated" juxtafacet cysts is reported. We emphasize the clinical and radiological aspects leading to diagnosis. We also discuss the results of the surgical treatment. MATERIAL AND METHODS: Medical information and radiological studies involving 28 patients were analyzed. Each patient has been operated on by decompressive laminectomy and resection of the cyst. The diagnosis was always confirmed by a pathological examination. The cyst most frequently occurred at the L4-L5 level (n = 18), and seldom at the L5-S1 (n - 6) or L3-L4 (n - 4) levels. RESULTS: The differential diagnosis from other pathological causes responsible for a radicular compression could not be done by physical examination. Spine X-rays or myelogram were nonspecific. Computed Tomography or CT-myelography could help in the diagnosis but MR imaging was the most sensitive. In our series, the respective sensitivities of these techniques are 56, 42 and 77%. The preoperative diagnosis was correct in 18 patients (64%). The cyst was sometimes adherent to the underlying dura, then significantly increasing the risk of dural tear and spinal fluid leak, especially when located at L3-L4 level. Surgical ablation lead to a complete recovery or an important improvement in 26 patients. CONCLUSIONS: The diagnosis of the juxtafacet cyst of the lumbar spine is better achieved by MRI. Surgery is the gold standard treatment, safe and long-term effective. When a total cyst removal with an internal facetectomy are performed, recurrence is exceptional.

Adult↗
PubMed2001

Differences between men and women in compliance with risk factor reduction: before and after coronary artery bypass surgery.

The purpose of this study was to determine whether a difference exists between genders in compliance to a heart-healthy lifestyle and whether the stress of coronary artery bypass graft (CABG) surgery caused one of the genders to become more compliant. A convenience sample of 30 men and 30 women who had CABG surgery at least 1 year earlier and were enrolled in a follow-up program through a cardiovascular surgeon's office were interviewed to assess coronary artery disease risk. The instrument used was the RISKO Heart Hazard Appraisal Tool. Preoperative records were also reviewed with the same tool to assess a person's preoperative risk. The research design used was 2 x 2 repeated measures. Data were analyzed with 2 x 2 repeated measures analysis of variance (ANOVA). Two findings were discovered. First, a statistically significant difference exists between men and women (F = 5.82 P =.019), with men scoring lower RISKO scores than women, indicating lower cardiovascular risk and better compliance to a healthy lifestyle, both before and after surgery. Second, a significant difference exists between preoperative and postoperative RISKO scores in the total population (F = 8.77 P =.004). Postoperative RISKO scores were lower, indicating an improvement in cardiovascular risk. The risk factors assessed are applicable to both heart disease and peripheral vascular disease.

Adult↗
PubMed1999

Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.

Adolescent↗
PubMed1999

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗
PubMed1999

Proteolytic cleavage of the amino terminus of the U(L)15 gene product of herpes simplex virus type 1 is coupled with maturation of viral DNA into unit-length genomes.

The U(L)15 gene of herpes simplex virus type 1 (HSV-1), like U(L)6, U(L)17, U(L)28, U(L)32, and U(L)33, is required for cleavage of concatameric DNA into genomic lengths and for packaging of cleaved genomes into preformed capsids. A previous study indicated that the U(L)15 gene encodes minor capsid proteins. In the present study, we have shown that the amino-terminal 509 amino acids of the U(L)15-encoded protein are sufficient to confer capsid association inasmuch as a carboxyl-terminally truncated form of the U(L)15-encoded protein with an M(r) of approximately 55,000 readily associated with capsids. This and previous studies have shown that, whereas three U(L)15-encoded proteins with apparent M(r)s of 83,000, 80,000, and 79,000 associated with wild-type B capsids, only the full-length 83,000-M(r) protein associated with B capsids purified from cells infected with viruses lacking functional U(L)6, U(L)17, U(L)28, U(L)32, and U(L)33 genes (B. Salmon and J. D. Baines, J. Virol. 72:3045-3050, 1998). Thus, all viral mutants that fail to cleave viral DNA into genomic-length molecules also fail to produce capsid-associated U(L)15 80,000- and 79,000-M(r) proteins. In contrast, the 80,000- and 79,000-M(r) proteins were readily detected in capsids purified from cells infected with a U(L)25 null virus that cleaves, but does not package, DNA. The conclusion that the amino terminus of the 83,000-M(r) protein is truncated to produce the 80,000- and/or 79,000-M(r) protein was supported by the following observations. (i) Whereas the C termini of the 83,000-, 80, 000-, and 79,000-M(r) proteins are identical, immunoreactivity dependent on the first 35 amino acids of the U(L)15 83,000-M(r) protein was absent from the 80,000- and 79,000-M(r) proteins. (ii) The 79,000- and 80,000-M(r) proteins were detected in capsids from cells infected with HSV-1(U(L)15M36V), an engineered virus encoding valine rather than methionine at codon 36. Thus, initiation at codon 36 is unlikely to account for production of the 80,000- and/or 79, 000-M(r) protein. Taken together, these data strongly suggest that capsid-associated U(L)15-encoded protein is proteolytically cleaved near the N terminus and indicate that this modification is tightly linked to maturation of genomic DNA.

DNA, Viral↗
PubMed1998

The herpes simplex virus 1 UL 17 gene is required for localization of capsids and major and minor capsid proteins to intranuclear sites where viral DNA is cleaved and packaged.

In nuclei of cells infected with herpes simplex virus (HSV), synthesized viral DNA accumulates as concatamers that are cleaved into genomic lengths and inserted into preformed capsids. Whereas newly replicated DNA and enzymes required for DNA synthesis accumulate in sites of infected cell nuclei termed replication compartments, the intranuclear site of DNA cleavage and packaging is currently controversial. DNA packaging requires the UL6, UL15, UL17, UL25, UL28, UL32, and UL33 genes in addition to the major capsid proteins. Using confocal immunofluorescence microscopy, it was observed that in > 95% of HEp-2 cells fixed at late times after infection with wild-type HSV-1, capsids, major capsid proteins ICP5 and ICP35, and the UL6-encoded minor capsid protein localized in DNA replication compartments. These data support the hypothesis that capsid assembly and DNA cleavage/packaging normally occur in HEp-2 cell replication compartments. In contrast, cells infected with a viral mutant lacking functional UL17 contained antigenically dense nuclear aggregates that stained with ICP35, ICP5, and capsid specific antibodies. Cells infected with the UL17 mutant virus also displayed UL6-specific fluorescence in a diffuse pattern at the nuclear periphery in regions not containing ICP35 and ICP5. Displacement of ICP35 from replication compartments was not observed in cells infected with cleavage/packaging mutants lacking UL28 and UL33. We conclude that the UL17 gene is required for correct targeting of capsids and major and minor capsid proteins to the DNA replication compartment of HEp-2 cells and deduce that this targeting reflects one functional role of UL17 in viral DNA cleavage and packaging.

Animals↗
PubMed1998

Herpes simplex virus DNA cleavage and packaging: association of multiple forms of U(L)15-encoded proteins with B capsids requires at least the U(L)6, U(L)17, and U(L)28 genes.

The U(L)15 gene of herpes simplex virus (HSV) is one of several genes required for the packaging of viral DNA into intranuclear B capsids to produce C capsids that become enveloped at the inner nuclear membrane. A rabbit antiserum directed against U(L)15-encoded protein recognized three proteins with apparent Mrs of 79,000, 80,000, and 83,000 in highly purified B capsids. The 83,000-Mr protein was detected in type C capsids and comigrated with the product of a U(L)15 cDNA transcribed and translated in vitro. The 83,000- and 80,000-Mr proteins were readily detected in purified virions. Inasmuch as (i) none of these proteins were detectable in capsids purified from cells infected with HSV-1(deltaU(L)15), a virus lacking an intact U(L)15 gene, and (ii) corresponding proteins in capsids purified from cells infected with a recombinant virus [HSV-1(R7244), containing a 20-codon tag at the 3' end of U(L)15] were decreased in electrophoretic mobility relative to the wild-type proteins, we conclude that the proteins with apparent Mrs of 83,000, 80,000, and 79,000 are products of U(L)15 with identical C termini. The 79,000-, 80,000-, and 83,000-Mr proteins remained associated with B capsids in the presence of 0.5 M guanidine HCl and remained detectable in capsids treated with 2.0 M guanidine HCl and lacking proteins associated with the capsid core. These data, therefore, indicate that U(L)15-encoded proteins are integral components of B capsids. Only the 83,000-Mr protein was detected in B capsids purified from cells infected with viruses lacking the U(L)6, U(L)17, or U(L)28 genes, which are required for DNA cleavage and packaging, suggesting that capsid association of the 80,000- and 79,000-Mr proteins requires intact cleavage and packaging machinery. These data, therefore, indicate that capsid association of the 80,000- and 79,000-Mr U(L)15-encoded proteins reflects a previously unrecognized step in the DNA cleavage and packaging reaction.

Animals↗
PubMed1998

The herpes simplex virus type 1 U(L)17 gene encodes virion tegument proteins that are required for cleavage and packaging of viral DNA.

Previous studies have suggested that the U(L)17 gene of herpes simplex virus type 1 (HSV-1) is essential for virus replication. In this study, viral mutants incorporating either a lacZ expression cassette in place of 1,490 bp of the 2,109-bp U(L)17 open reading frame [HSV-1(deltaU(L)17)] or a DNA oligomer containing an in-frame stop codon inserted 778 bp from the 5' end of the U(L)17 open reading frame [HSV-1(U(L)17-stop)] were plaque purified on engineered cell lines containing the U(L)17 gene. A virus derived from HSV-1(U(L)17-stop) but containing a restored U(L)17 gene was also constructed and was designated HSV-1(U(L)17-restored). The latter virus formed plaques and cleaved genomic viral DNA in a manner indistinguishable from wild-type virus. Neither HSV-1(deltaU(L)17) nor HSV-1(U(L)17-stop) formed plaques or produced infectious progeny when propagated on noncomplementing Vero cells. Furthermore, genomic end-specific restriction fragments were not detected in DNA purified from noncomplementing cells infected with HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop), whereas end-specific fragments were readily detected when the viruses were propagated on complementing cells. Electron micrographs of thin sections of cells infected with HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop) illustrated that empty capsids accumulated in the nuclei of Vero cells, whereas DNA-containing capsids accumulated in the nuclei of complementing cells and enveloped virions were found in the cytoplasm and extracellular space. Additionally, protein profiles of capsids purified from cells infected with HSV-1(deltaU(L)17) compared to wild-type virus show no detectable differences. These data indicate that the U(L)17 gene is essential for virus replication and is required for cleavage and packaging of viral DNA. To characterize the U(L)17 gene product, an anti-U(L)17 rabbit polyclonal antiserum was produced. The antiserum reacted strongly with a major protein of apparent Mr 77,000 and weakly with a protein of apparent Mr 72,000 in wild-type infected cell lysates and in virions. Bands of similar sizes were also detected in electrophoretically separated tegument fractions of virions and light particles and yielded tryptic peptides of masses characteristic of the predicted U(L)17 protein. We therefore conclude that the U(L)17 gene products are associated with the virion tegument and note that they are the first tegument-associated proteins shown to be required for cleavage and packaging of viral DNA.

Animals↗
PubMed1995

Bronchial responsiveness in the neonatal period as a risk factor for wheezing in infancy.

Bronchial responsiveness is closely associated with asthma in schoolchildren. We wished to test the hypothesis that bronchial responsiveness in the neonatal period might be a risk factor for lower-respiratory illnesses (LRI), typically cough and wheezing with viral infection, in infants. A cohort of 73 full-term healthy infants of atopic parents were observed during the first year of life. Respiratory illness was recorded and ascertained retrospectively by questionnaires administered to parents at 6-mo intervals, and infants were classified as having: LRI (one or more episode of wheezing in the first year) or no LRI (no wheezing). At approximately 1 mo of age, lung function was measured under sedation, and bronchial responsiveness (BR) to histamine aerosol was determined and expressed as PC30, the provocative concentration of histamine that induced a 30% decrease in maximum flow at FRC (V'maxFRC) by the squeeze technique. For the whole group, no index of lung function predicted subsequent wheezing. Among boys, however, there was a trend toward a lower V'maxFRC in those who subsequently developed LRI than in the group without LRI (median values 62 versus 98 ml/s; 95% CI: -1 to 68; p = 0.06), while among girls the major difference was in PC30, for which those who subsequently had LRI were significantly more responsive as neonates (PC30 was lower) than the group without LRI (1.4 versus 8.3 g/L; 95% CI: 1.0 to 13.1; p < 0.05). These findings suggest that sex differences in airway structure and responsiveness present soon after birth, and representing differences in fetal lung development, are associated with differences in the risk of subsequent LRI with wheezing.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial Hyperreactivity↗
PubMed1993

Genomic MHC haplotyping of mutant cell lines using a novel marker.

The aim of this study was to characterize MHC mutant cell lines by studying haplospecific markers within the MHC and specifically in the 250 kilobase (kb) region between the HLA B and TNF loci. This region has been difficult to define because of the lack of appropriate markers. Spontaneous MHC mutants were isolated after immunoselection with an anti-HLA A2 monoclonal antibody and complement. Ten mutants were characterized using serological or allelic and genomic DNA markers within the HLA A to HLA DQ region of the MHC. Most mutants lost at least the 3 megabases of DNA from HLA A to HLA DQ viz the whole haplotype carrying HLA A2. Variants which have lost either HlA A alone or HLA A and HLA B were also found. The results show that it is possible to map the extent of the deletion between HLA B and TNF. Haplospecific scanning patterns for the CL region appear particularly useful.

Cell Line↗
PubMed1990

How much aerosol reaches the lungs of wheezy infants and toddlers?

Using sodium cromoglycate as a non-toxic marker, we assessed the delivery of aerosol to nine wheezy infants and seven healthy adults. The drug was delivered to the infants by face mask and spacer device from a metered dose inhaler, and by face mask and nebuliser to the infants and the adults who breathed though their noses. The concentration of sodium cromoglycate was estimated in timed urine collections to find out how much of the dose was absorbed from the lung. Only 0.13% to 0.61% of the 20 mg nominal dose was detected in the urine, representing an estimated 0.3% to 1.5% deposited in the lung. Nasal filtration of aerosol could be a critical factor in reducing lung deposition.

Absorption↗
PubMed1986

Frontoethmoidectomy in the treatment of mucoceles. A neglected operation.

The treatment of mucoceles by the Lynch-Howarth frontoethmoidectomy has been criticized because of a high rate of recurrence and postoperative complications. The long-term results in 60 patients treated by this method are examined to evaluate these criticisms. Compared with the osteoplastic flap-obliterative procedure, our results suggest a much lower recurrence rate (4%) and considerably better cosmesis with frontoethmoidectomy. This is achieved by the use of a fenestrated Silastic drainage tube left in place for five months and careful positioning of the scar. The criticisms would appear to be unjustified, and these results lend support to the continued use of the Lynch-Howarth procedure in the treatment of frontoethmoidal mucoceles.

Adolescent↗
PubMed1986

Acute respiratory infections: a longitudinal study of 151 children in Burkina-Faso.

A longitudinal study of 151 children under five years of age was performed in a rural village of Burkina-Faso (West Africa). During systematic examinations by a physician during the rainy season, 44% of the children were found to be ill and 59% of these had an acute respiratory infection (ARI). During the dry season, the rates were 48% and 73% respectively. Weekly interviews by a field worker showed 6.2 attacks of ARI during the six months of the rainy season and 7.0 during the six months of the dry season. Risk factors for ARI were malnutrition assessed by arm circumference, and a high birth rank. At the 'field-dispensary', ARI accounted for 41% of the visits; lower respiratory infections (LRI) accounted for 24%, similar to the proportion of LRI among illnesses found during the systematic examination.

Acute Disease↗