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S Boyle

Publications and source records attributed to S Boyle.

At least 55 records · Page 3Linked to original sources
PubMed1995

A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.

We describe a detailed physical map of human chromosome 11, extending from the distal part of p13 through the entirety of p14 to proximal p15.1. The primary level of mapping is based on chromosome breakpoints that divide the region into 20 intervals. At higher resolution YACs cover approximately 12 Mb of the region, and in many places overlapping cosmids are ordered in contiguous arrays. The map incorporates 18 known genes, including precise localization of the GTF2H1 gene encoding the 62-kDa subunit of TFIIH. We have also localized four expressed sequences of unknown function. The physical map incorporates genetic markers that allow relationships between physical and genetic distance to be examined, and similarly includes markers from a radiation hybrid map of 11. The cytogenetic location of cosmids has been examined on high-resolution banded chromosomes by fluorescence in situ hybridization, and FLpter values have been determined. The map therefore fully integrates physical, genic, genetic, and cytogenetic information and should provide a robust framework for the rapid and accurate assignment of new markers at a high level of resolution in this region of 11p.

Base Sequence↗
PubMed1995

Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype.

Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families.

Aniridia↗
PubMed1995

Direct microdissection and microcloning of a translocation breakpoint region, t(1;11)(q42.2;q21), associated with schizophrenia.

We describe the generation of large-fragment microclone libraries from the chromosomal breakpoint of a reciprocal balanced translocation linked to schizophrenia. The abnormality was visible under the phase-contrast microscope, allowing direct dissection from unstained, unbanded metaphases. Two separate microdissection experiments yielded 443 and 672 recombinants, respectively. Following complete EcoRI digestion, inserts with an average size of 0.3 kb (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15-6.5 kb) in the second. FISH analysis of pooled clones "painted" back onto the derivative chromosome and assignment of microclones to somatic cell hybrids confirmed the fidelity of the method. Microdissection of chromosome regions identified by karyotype rearrangements in unstained, unbanded metaphases is a potentially powerful tool for positional cloning.

Base Sequence↗
PubMed1995

Multiple sclerosis progression in a natural history study: predictive value of cerebrospinal fluid free kappa light chains.

OBJECTIVES: To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures. BACKGROUND: CSF immune abnormalities are common in MS but have not been linked to disease progression. DESIGN METHODS: Thirty-six patients with definite (n = 28), probable (n = 2), or possible (n = 6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length of follow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models. RESULTS: By 36 months, 33% (95% CI = 10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% CI = 27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p = 0.04) and 9HT (Hazard Ratio 10.77, p = 0.04). CONCLUSIONS: In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.

Adolescent↗
PubMed1994

Organization of the region encompassing the human serum amyloid A (SAA) gene family on chromosome 11p15.1.

The four members of the human serum amyloid A protein (SAA) gene family are clustered on human chromosome 11p15.1. Three genes are differentially expressed and encode small apolipoproteins of M(r) 12-19 kDa: SAA1 and SAA2 encode the acute phase SAAs (A-SAAs), and SAA4 encodes the constitutively expressed SAA (C-SAA). A fourth locus, SAA3, is a pseudogene. The human SAA gene family encompasses approximately 150 kb contained on a 900-kb yeast artificial chromosome contig. SAA1 and SAA2 are 15-20 kb apart and are arranged in divergent transcriptional orientations. SAA4 is 9 kb downstream of SAA2 and in the same orientation. SAA3 is 110 kb downstream of SAA4, and its relative orientation could not be determined. All genes known to be in the same human and mouse syntenic linkage group as SAA were mapped within the contig. Interphase FISH was used to orientate the region relative to the centromere: cen-LDHC-LDHA-SAA1-SAA2-SAA4-SAA3-TP H-D11S18- KCNC1-MYOD1-pter.

Animals↗
PubMed1994

Finding the facts.

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Costs and Cost Analysis↗
PubMed1994

Condensation behaviour of the human X chromosome in male germ cells and Sertoli cells examined by fluorescence in situ hybridization.

The chromatin condensation behaviour of the human X chromosome has been studied by fluorescence in situ hybridization (FISH) analysis in germ cells and Sertoli cells of the adult testis, and comparisons are made with previous findings for the human Y chromosome and for chromosome 7. In meiotic prophase, the X chromosome can be seen to extend greatly at zygotene and to contract through pachytene into the sex vesicle. Such extension, which has also been noted for the human Y chromosome at this stage of meiosis, could be a prerequisite for XY pairing and crossing-over. By in situ hybridization analysis, the sex chromosomes of patients with 'Sertoli-cell-only' syndrome appear extremely contracted compared with the normally extended state of those in adult Sertoli cells of fertile men. By contrast, the state of expansion for chromosome 7 in Sertoli cells appears identical for sterile and fertile testes. This could suggest an association between gene-controlled germ cell losses and failure of expansion of the sex chromosome axes. The variable patterns of extension and contraction for the X and Y chromosome axes in germ cells and Sertoli cells might provide underlying clues to patterns of expression noted for sex-linked genes in the human testis.

Adult↗
PubMed1994

Rational design of high affinity tachykinin NK2 receptor antagonists.

The rational discovery of a high affinity NK2 receptor antagonist is described utilizing a general strategy for peptoid design. The contribution to NK2 receptor binding affinity for each amino acid of the hexapeptide 'minimum fragment': Leu-Met-Gln-Trp-Phe-GlyNH2 (8c), was examined by preparing derivatives where each amino acid in turn was replaced with Ala in an 'alanine scan'. The results from this study indicated the primary importance of the Trp and Phe side-chain for binding and led to the observation that Z-Trp-PheNH2 (9a) is a micromolar affinity NK2 receptor dipeptide lead. Further exploration of structure-affinity via conformationally restricted analogues and N- and C-terminus modifications gave a selective, nanomolar affinity NK2 receptor antagonist, (2,3di-CH3OPh)CH2OCO(S)Trp(S)alpha-MePheGlyNH2, PD 147714 (19) with an K(i) = 1.4 nM (hamster urinary bladder membranes and using [125I]-iodohistidyl-NKA (0.1 nM) as the radioligand).

Amino Acid Sequence↗
PubMed1994

Rational design of high affinity tachykinin NK1 receptor antagonists.

The rational design of a non-peptide tachykinin NK1 receptor antagonist, [(2-benzofuran)-CH2OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH3)P h (28, PD 154075) is described. Compound 28 has a Ki = 9 and 0.35 nM for the NK1 receptor binding site in guinea-pig cerebral cortex membranes and human IM9, cells respectively (using [125I] Bolton-Hunter-SP as the radioligand). It is a potent antagonist in vitro where it antagonises the contractions mediated by SPOMe in the guinea-pig ileum (KB = 0.3 nM). Compound 28 is active in vivo in the guinea-pig plasma extravasation model, where it is able to block the SPOMe-induced protein plasma extravasation (monitored by Evans Blue) in the bladder with an ID50 of 0.02 mg kg-1 iv.

Animals↗
PubMed1994

Cutaneous sarcoid-like granulomas in primary immunodeficiency disorders.

We report the occurrence of cutaneous sarcoid-like granulomas in one patient with common variable immunodeficiency and another with 'thymoma and hypogammaglobulinaemia'. To our knowledge, this is the first time that such skin lesions have been described in patients with primary immunodeficiency. These granulomas may be attributed to a combination of interleukin-2 deficiency and a profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular eruption' associated with human immunodeficiency virus infection, and might reflect a common pathogenic mechanism.

Adult↗
PubMed1993

Ghostbusters.

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Fees, Medical↗
PubMed1993

Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: analysis by stage, immunophenotype, and morphology.

Fluorescence in situ hybridization (FISH) with a chromosome 12 specific alpha-centromeric probe was performed on interphase cells from 183 patients with B-cell chronic lymphocytic leukemia (CLL). Twenty one cases with trisomy 12 (11.5%) were detected. The number of trisomic cells ranged from 5.5% to 76% (mean 38.5%). No correlation was found between the presence of trisomy 12 and white blood cell count, hemoglobin level, platelet count, a specific immunophenotype, clinical stage, sex, splenomegaly, or lymphadenopathy. Morphologic review of all cases with trisomy 12 showed seven (33%) with more than 10% prolymphocytes and three (14%) with CLL of mixed cell type. While trisomy 12 is the most common chromosomal abnormality in CLL, it is more frequent in morphologically atypical cases, some of which may be undergoing transformation. There was a statistically significant difference in the incidence of atypical cases between those with (47%) and without (7.6%) trisomy 12 (P < .001). It remains to be determined whether this abnormality is associated with a worse prognosis; this is currently being investigated in the context of a national therapeutic trial. The technique used is more sensitive than conventional cytogenetic analysis, which in this series failed to detect trisomy 12 in six cases. FISH allows the systematic study on a large number of patients without the need of metaphase preparations.

Antigens, CD↗
PubMed1993

Intraoperative assessment of nodal status in the selection of patients with breast cancer for axillary clearance.

Preliminary axillary node sampling with intraoperative reporting of imprint cytology to detect positive nodes was assessed in 50 consecutive patients with T1 or T2 breast cancer undergoing axillary clearance, 21 of whom were histologically node positive. A mean of 3.5 (range 1-4) nodes were sampled. Axillary clearance yielded a mean of 11.7 (range 4-32) nodes. Of node-positive patients, sampled nodes detected 18 of 21 on immediate processing, one on subsequent paraffin sections, and failed to detect two (one of ten and one of 17 positive nodes). If the technique had been used during operation to select patients for axillary clearance, 29 of 50 would have avoided the operation, one of two node-positive patients would have required delayed axillary treatment and two of 21 with minimal axillary disease would not have received further axillary treatment or adjuvant therapy. The technique may be useful in reducing the morbidity of breast cancer surgery without increasing the risk of locoregional or distant recurrence.

Adult↗
PubMed1993

Voices of fear and anxiety and sadness and depression: the effects of speech rate and loudness on fear and anxiety and sadness and depression.

Two studies investigated the role of expressive vocal behavior (specifically, speech rate and loudness) in fear and anxiety and in sadness and depression. In the first study, participants spoke about personally experienced fear and anxiety-arousing and neutral events using 3 different voice styles: fast and loud, normal, and slow and soft. In the second study, participants spoke about personally experienced sad or depressing and neutral events using the same 3 voice styles. In both studies, the participants' highest levels of subjective affective and cardiovascular (CV) arousal occurred when they spoke about the emotional events in a mood-congruent voice style: fast and loud in the case of fear and anxiety, and slow and soft in the case of sadness or depression. Mood-incongruent voice styles canceled the heightened levels of CV arousal normally associated with these negative emotions. The voice-style manipulation had no significant effect on the participants' levels of CV arousal during the neutral discussions.

Adult↗
PubMed1992

Dimensions of anger-hostility and cardiovascular reactivity in provoked and angered men.

This study investigated the relationship between two dimensions of anger-hostility--the expression of anger-hostility and the experience of anger-hostility--and cardiovascular reactivity in provoked and angered men. A serial subtraction task was administered to 41 male undergraduates who were provoked and angered. A measure of the expression of anger-hostility correlated positively and significantly with systolic and diastolic blood pressure (BP) reactivity. There were no significant correlations between a measure of the experience of anger-hostility and cardiovascular reactivity. The two types of anger-hostility were also found to relate differentially to life-style variables that have been identified as risk factors for coronary heart disease (CHD), with only the expression of anger-hostility showing positive relationships with these life-style CHD risk factors. These findings are discussed within the context of a similar differential relationship between the two dimensions of anger-hostility and CAD and CHD. Finally, significant negative relationships were obtained between the experience of anger-hostility and resting BP and heart rate levels. These findings are discussed within the context of other data suggesting that trait anxiety-neuroticism may have protective properties.

Adult↗
PubMed1991

Warts and all.

If the government wishes to promote minor surgery in general practice as an alternative to hospital care, it must demonstrate a much greater commitment to the task, argue Chris Smaje, Sean Boyle and Rosemary Beardow.

England↗
PubMed1991

Biological properties of RB51; a stable rough strain of Brucella abortus.

A rifampin-resistant mutant of Brucella abortus, designated RB51, was derived by repeated passage of strain 2308 on Trypticase soy supplemented with 1.5% agar and varying concentrations rifampin or penicillin. The RB51 colonies absorbed crystal violet and RB51 cell suspensions autoagglutinated, indicating a rough type colonial morphology for this strain. No O-chain component was detected in lipopolysaccharide (LPS) extracted from RB51 on SDS-PAGE gels stained with silver. Western blot analysis with the monoclonal antibody BRU 38, which is specific for the perosamine homopolymer O-chain of smooth Brucella LPS, indicated that the LPS of RB51 is highly deficient in O-chain when compared with the parenteral smooth strain 2308 or rough strain 45/20. Biochemically, RB51 resembles parental strain 2308 in its ability to utilize erythritol. Intraperitoneal inoculation of RB51 into mice results in a splenic colonization which is cleared within four weeks post infection. RB51 does not revert to smooth colony morphology upon passage in vivo (mice) or in vitro. Mice infected with RB51 produce antibodies against B. abortus antigens including class 2 and 3 outer membrane proteins but not against the O-chain. Furthermore, rabbits, goats and cattle hyperimmunized with sonicates of RB51 develop antibodies to B. abortus cellular antigens but do not develop antibodies specific for the O-chain. Immunization of mice with 1 x 10(8) viable RB51 organisms confers significant protection against challenge with virulent B. abortus strain 2308.

Animals↗