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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 199 records · Page 11Linked to original sources
PubMed1994

Multiple DNA variant association analysis: application to the insulin gene region in type I diabetes.

Association and linkage studies have shown that at least one of the genetic factors involved in susceptibility to insulin-dependent diabetes mellitus (IDDM) is contained within a 4.1-kb region of the insulin gene. Sequence analysis has led to the identification of 10 DNA variants in this region that are associated with increased risk for IDDM. These variants are in strong linkage disequilibrium with each other, and previous studies have failed to distinguish between the variant(s) that cause increased susceptibility to IDDM and others that are associated with the disease because of linkage disequilibrium. To address this problem, we have undertaken a large population study of French diabetics and controls and have analyzed genotype patterns for several of the variant sites simultaneously. This has led to the identification of a subset consisting of four variants (-2733AC, -23HphI, -365VNTR, and +1140AC), at least one of which appears to be directly implicated in disease susceptibility. The multiple-DNA-variant association-analysis approach that is applied here to the problem of identifying potential susceptibility variants in IDDM is likely to be important in studies of many other multifactorial diseases.

Diabetes Mellitus, Type 1↗
PubMed1993

Collagen-linked fluorescence in human atherosclerotic plaques.

Advanced glycosylation endproducts (AGE) are intraprotein crosslinks which form in the late stages of the Maillard (browning) reaction. It is unknown whether local changes in AGE-modified collagen occur within arteries. We measured AGE-modified collagen as collagen-linked fluorescence (CLF) in human arterial tissue and in various forms of atherosclerotic plaque. All tissues showed single fluorescence peak at excitation wavelength 340 nm and emission wavelength 420-440 nm. CLF in the aorta was 27.9 +/- 8.5 units/mg, in the coronary arteries 25.9 +/- 6.3 units/mg and in the tendon 47.8 +/- 11.5 units/mg. CLF in the skin correlated with CLF in the aorta (r = 0.467, P = 0.025) but not with CLF in coronary arteries (P = 0.935). In areas of aorta covered by superficial plaque, CLF was decreased compared with adjacent, atheroma-free segments (22.2 +/- 5.2 units/mg vs. 27.9 +/- 8.5 units/mg; P = 0.01). The CLF of collagenous plaques correlated with CLF of the atheroma-free regions. Individuals with low to moderate atheroma had lower (20.0 units/mg) CLF in superficial atherosclerotic plaques than patients with severe atheroma (22.5 units/mg; P = 0.0466). Our results indicate that local changes in vascular AGE-collagen concentration occur in atherosclerosis. This finding may have pathogenetic significance in atherosclerosis.

Aged↗
PubMed1993

Systematic study of human alpha beta T cell receptor V segments shows allelic variations resulting in a large number of distinct T cell receptor haplotypes.

The variation of the alpha beta T cell receptor (TCR) results mainly from rearrangements of germ-line V, D and J elements combined with the processes of N- and P-region addition. In addition to this extensive diversity, diallelic polymorphism is also recognized in V regions of beta loci. Four such polymorphisms have previously been defined, but the full extent of such variation has not yet been established. To investigate allelic polymorphism, we used a strategy based V locus-specific polymerase chain reaction and single-strand conformation polymorphisms. Studying the two V beta 2 loci and the V alpha 8.1 locus, we found that all exhibited a coding polymorphism. One of the V beta 2 loci proved to be the first multiallele segment to be recognized, with three common variants. The second V beta 2 locus, for which none of the two alleles has been identified in cDNA, appeared in fact to be a V beta orphon, in abnormal location on the chromosome 9. A yeast artificial chromosome containing part of the TCRB locus allowed us to place the first V beta 2 segment on the known map to define haplotypes with two other polymorphic segments: V beta 1 and V beta 6.7. Multiple distinct haplotypes result from combinations between these polymorphic loci, showing that V beta regions are highly variable between individuals. Two alleles exist at the V alpha 8.1 segment and both are expressed. This represents the first example of a frequent coding polymorphism for TCRA gene. The distribution of allele frequencies for these segments suggest the action of balancing selection. These data add a further dimension to TCR polymorphism and suggest new candidates to explore TCR-encoded susceptibility to autoimmune diseases.

Alleles↗
PubMed1993

KIM185, a monoclonal antibody to CD18 which induces a change in the conformation of CD18 and promotes both LFA-1- and CR3-dependent adhesion.

Unactivated peripheral blood leukocytes show little tendency to bind to other cells or matrix components, whilst, in the presence of inflammatory mediators, adhesive interactions can rapidly increase. The Leu-CAM (beta 2 integrin) family of adhesion molecules have been shown to mediate a variety of these induced adhesion events. Here we describe a monoclonal antibody against CD18, KIM185, which stimulates JY cell homotypic aggregation by a CD11 a pathway as well as inducing the adherence of neutrophils to protein-coated plastic by a CD11b-dependent mechanism. The antibody recognizes an epitope distinct from the previously described KIM127 antibody and evidence is presented that the binding of KIM185 can cause a change in the conformation of the CD18 molecule.

Antibodies, Monoclonal↗
PubMed1993

Development of human fetal lung in organ culture compared with in utero ontogeny.

In utero, at around 23 wk gestation, the progenitor epithelium of distal airway differentiates into type I and type II pneumatocytes. Human fetal lung organ cultures, as early as 12 wk gestation, have the competence to self-differentiate. Distal airway epithelial immunoreactivity to cytokeratins CK 7, 8, and 18 decreases with differentiation both in utero and in organ culture, whereas reactivity to epithelial membrane antigen remains constant in both. As distal airways dilate, the mean percentage airspace of fetal lungs in organ culture increases to 58%, equivalent to lung of gestation 26.0 +/- 7.3 wk. In organ culture, capillary blood vessels, visualized by vimentin immunoreactivity, remodel and more closely approximate the epithelium but without direct invasion. In utero, at 23 wk gestation, elastin appears as condensation around airways and forms a basis for secondary crests which, by 29 wk gestation, evolve into alveolar septae. In organ culture, no elastin is deposited, no secondary or alveolar crests form, and the lung retains a simple saccular structure. Differentiation of the terminal airway epithelium and mesodermal maturational events to facilitate gas exchange, such as capillary invasion or secondary-alveolar crest formation, are almost synchronous in human lung in utero but clearly dissociate in organ culture.

Analysis of Variance↗
PubMed1993

Identification and characterization of [125I]arginine vasopressin binding sites on human peripheral blood mononuclear cells.

Arginine vasopressin (AVP) is a nonapeptide that has been shown to be released from the posterior pituitary during stress. Although noted primarily for its hemodynamic and homeostatic properties, AVP also appears to have an effect on the immune system. It may modulate cellular immunity via its enhancement of the autologous mixed lymphocyte response (AMLR), an effect which we have demonstrated to occur over a wide dose range with a maximum at 10(-7) M. In this study, we examined the binding of [125I]AVP, and AVP analogues to human peripheral blood mononuclear cells (PBMC). AVP inhibited [125I]AVP (0.2 nM) binding on PBMC in a dose-dependent manner with maximal inhibition being reached at 10(-8) M. Specific [125I]AVP binding, as defined as that which could be displaced by 1 x 10(-6) M AVP, was saturable, time-dependent, and linear to cell concentration. Specific binding reached saturation at approximately 1000 pM in 45 minutes. From Scatchard analysis of saturation experiments it appeared to be a homogeneous population of binding sites with KD of approximately 0.5 nM and Bmax of approximately 7.6 fmole/8 x 10(6) cells, corresponding to approximately 527 binding sites/cell. There was a good correlation between AVP binding and cell number. AVP failed to dissociate completely from its binding sites in 60 minutes, perhaps because of the formation of a high-affinity ligand-binding site complex. From competitive binding studies with various AVP antagonists and analogues, it was found that the AVP binding site appeared to be V1-like. AVP binding occurred predominantly on B-cells and macrophages. Having provided evidence for the existence of specific, high affinity, and saturable V1-like AVP binding sites, we suggest a potential modulatory role for AVP in the communication between the neuroendocrine and immune systems.

Amino Acid Sequence↗
PubMed1993

Crime and drug use among applicants for methadone maintenance.

The relationship between crime and drug use was examined in 313 Australian opioid addicts who applied for entry to methadone treatment. More than 90% of them had recorded one or more convictions for property or drug offences. Subjects' self-reported convictions were moderately correlated with convictions recorded by the police. Men were more likely to begin their opioid use at or after their first criminal conviction, while women were more likely to begin offending after they used opioids. The rate at which subjects accrued convictions for property offences declined as they grew older and the earlier a subject's first exposure to the criminal justice system the higher the rate at which they accrued convictions.

Adult↗
PubMed1993

A deleted hobo element is involved in the unstable thermosensitive vg(al) mutation at the vestigial locus in Drosophila melanogaster.

We have described a new unstable mutant of the vestigial locus isolated from a natural population. From this mutant, vestigial(almost) (vg(al)), wild-type (vg(al+)), and extreme (vg(ext)), alleles arose spontaneously. The molecular analysis of vg(al) shows that the mutation is due to a 1874 bp hobo element inserted in a vestigial intron. Two distinct kinds of events lead a wild-type phenotype. Three independent vg(al+) alleles result from an excision of the hobo element and two other vg(al+) alleles have further deletions of hobo sequence. The sequence of one of them shows a 1516 bp hobo insertion at the same place and in the same orientation as the 1874 bp insertion. In the vg(ext) alleles, we found a 5' or 3' variably sized deletion of vg sequences. One of them, which has been cloned and sequenced, has a deletion finishing exactly at the left terminal repeat' hobo element. The genetic implications of these different genetic structures are discussed.

Alleles↗
PubMed1993

The reliability of Cancer Registry records.

Data from the Thames Cancer Registry were compared with data independently abstracted from medical records for 466 patients with confirmed cancer of the bladder diagnosed in 1982. High levels of agreement were observed for five continuous variables and for tumour morphology. Data concerning tumour stage did not clearly distinguish superficial from invasive tumours. Cancer registry data were found to be reliable except for tumour stage which may not be clearly documented in clinical records.

Carcinoma, Transitional Cell↗