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Biomedical subjects

G Vance

Publications and source records attributed to G Vance.

10 recordsLinked to original sources

Modification of T-cell receptor Vbeta repertoire in response to allergen stimulation in peanut allergy.

BACKGROUND: Peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis. Little is known of the immunologic mechanisms that underlie peanut allergy. OBJECTIVES: In this study we examined clonality of the T-cell response (TCR) to peanut in MHC class II identical, peanut allergy-discordant sibling pairs. METHODS: Four sibling pairs were investigated. The TCR repertoire was analyzed before and after in vitro stimulation of PBMCs with crude peanut or PHA, as control for general/nonspecific reactivity. Eighteen TCR-Vbeta families were examined by flow cytometry. Where significant differences in incidence of particular TCR-Vbeta families were observed, PCR familyspecific cDNA amplification and gene scanning were performed. RESULTS: After stimulation with peanut, no selective expansion of any TCR-Vbeta subpopulation was observed with flow cytometry, in either the peanut-allergic or nonallergic siblings, with the exception of 1 peanut-allergic subject who demonstrated a significant increase of TCR-Vbeta11(+) cells (0.3%-5.9% of the total CD3(+) cells). However, gene scanning revealed predominant single-size PCR products for TCRBV11 in all peanut-allergic subjects after peanut stimulation. TCRBV11 polyclo-nality was observed in allergic and nonallergic subjects before peanut stimulation and in nonallergic subjects after peanut stimulation. In comparison, all subjects, before and after stimulation with peanut, showed polyclonality for TCRBV2. CONCLUSIONS: Our results argue for clonal or oligoclonal TCRs to crude peanut and indicate that changes in the TCRBV11 subpopulation are restricted to peanut-allergic subjects after stimulation with crude peanut allergen.

Allergens↗

Toward quality assurance for metaphase FISH: a multicenter experience.

Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multicenter determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for small nuclear ribonucleoprotein polypeptide N (SNRPN) and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid, and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and two control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15)(q11.2-->q12) and 15 with normal #15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete, or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made, including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 min; slides processed in batches of 4 and analyzed singly required 36.9 min. We conclude that proficiency testing for FISH by using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.

Autoantigens↗

Toward quality assurance for metaphase FISH: a multi-center experience.

Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of clinical cytogenetics, no organization sponsors multi-center determinations of the efficacy of probes. We report on 23 laboratories that volunteered to provide slides and to use a probe for SNRPN and a control locus. Experiences with FISH for these laboratories during 1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic fluid and bone marrow. In an initial study of hybridization efficiency, the median percentage of metaphases from normal individuals showing two SNRPN and 2 control signals for slides prepared at each site was 97.0 (range = 74-100); for slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a subsequent blind study, each laboratory attempted to score 5 metaphases from each of 23 specimens [8 with del(15) (q11.2-->q12) and 15 with normal 15 chromosomes]. Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in 457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete or no results were reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1 made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to inexperience with FISH. The working time to process and analyze slides singly averaged 49.5 minutes; slides processed in batches of 4 and analyzed singly required 36.9 minutes. We conclude that proficiency testing for FISH using an extensive array of challenges is possible and that multiple centers can collaborate to test probes and to evaluate costs.

Humans↗

Ocular manifestations of Hansen's disease.

A detailed ophthalmic evaluation including slitlamp biomicroscopy, measurement of corneal sensitivity using Cochet and Bonnet aesthesiometer, Schirmer's test and Goldmann applanation tonometry was carried out in 89 patients of Hansen's disease attending the leprosy clinic with or without ocular symptoms and willing to undergo eye evaluation. Thirty-one patients had lepromatous leprosy (8 with erythema nodosum leprosum), 56 patients had borderline disease (13 with reversal reactions) and 2 had tuberculoid disease. In addition to the well documented changes of lagophthalmos (6.7%), uveitis (7.3%) and cataracts (19%), we noted prominent corneal nerves in 133 eyes (74.7%), beaded corneal nerves in 19 eyes (10.7%), corneal scarring in 10 eyes (5.6%), corneal hypoaesthesia in 51 eyes (28%) and dry eye in 18 eyes (13%). Beaded corneal nerves and/or stomal infiltrates occurred mainly in the lepromatous group (75%). Ocular hypotony (IOP less than 12 mm Hg) was not seen more frequently in Hansen's as compared to age and sex matched controls with refractive errors or cataracts (33.7%, vs. 37.8%, p = 0.33). Our study highlights the primary corneal involvement with corneal neuropathy as the predominant feature of Hansen's disease.

Adolescent↗

Some reflections on the phylogeny and function of the pineal.

The pineal gland is a universal feature of vertebrate organization and has been implicated in the control of rhythmic adaptations to daily and seasonal cycles. This paper considers three aspects of pineal function; the generation of a rhythmical endocrine signal (the nocturnal synthesis of melatonin) and the use of the signal in the regulation of circadian and photoperiodic functions. The shape of the nocturnal signal is determined by an interaction of afferent neural control and biochemical processes intrinsic to the pinealocyte. The nature of the effect of the signal upon circadian systems is unclear, and in adult mammals may not be a specific, direct influence upon the entrainment pathways of the oscillator. In the foetus, strong evidence exists for a physiological role of the maternal melatonin signal as a true internal zeitgeber, remnants of which may persist in the adult. Photoperiodic time measurement in adult and foetal mammals is critically dependent upon the melatonin signal. Indirect evidence indicates that several neural systems may be involved in the response to melatonin and consistent with this, a variety of central melatonin binding sites have been identified in the brain and pituitary. The intra-cellular actions of melatonin and the properties of melatonin responsive neural systems have yet to be identified, but in the context of photoperiodic time measurement, it is clear that the neural responses to melatonin are not dependent upon the circadian clock. The two central effects of melatonin; photoperiodic time measurement and circadian entrainment are probably mediated through completely separate mechanisms.

Animals↗

Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6.

Inherited spinocerebellar ataxias (SCA) are progressively degenerative neurological diseases. The primary site of degeneration is the cerebellar cortex--in particular, the Purkinje cells. In the present report, the SCA locus, inherited as an autosomal dominant trait in a large kindred, is localized to a region approximately 15 centimorgans telomeric of HLA-A on the short arm of chromosome 6.

Chromosome Mapping↗

Coping with aversive stimulation in the neonatal period: quiet sleep and plasma cortisol levels during recovery from circumcision.

Measures of behavioral state and plasma cortisol were obtained on 80 healthy, full-term, 2-3-day-old, male newborns who were scheduled to be circumcised. To establish baseline or precircumcision levels, the newborns were observed, and behavioral state was recorded for the half hour prior to circumcision. Blood was sampled via heelstick for plasma cortisol determination at the end of this observation period. The newborns were then circumcised and assigned randomly to one of 4 postcircumcision, blood-sampling time-point groups. The time points were 30, 90, 120, and 240 min following the beginning of circumcision. Behavioral state was observed during circumcision and for the half hour prior to taking the second blood sample. The results showed a return to baseline cortisol levels sometime prior to 240 min, with data from an additional group of 10 newborns indicating that the return occurred by 150 min. Behavioral distress during circumcision was associated with elevations in plasma cortisol at 30 and 90 min. Quiet sleep was correlated negatively with plasma cortisol prior to circumcision, and significant increases in quiet sleep followed circumcision, with the greatest increase corresponding to the period of most rapid reductions in cortisol.

Adaptation, Psychological↗