Assessment of the influence of HLA class I and class II loci on the prevalence of keloid disease in Jamaican Afro-Caribbeans.

Keloid disease (KD) is a common abnormal cutaneous fibrotic disorder of unknown aetiopathogenesis. KD is reported to have a strong genetic component as it is often familial and has a high incidence in certain ethnicities, in particular those of Afro-Caribbean origin. Genetic risk factors combined with aberrant lesional inflammatory responses point to the human leukocyte antigen (HLA) system as a viable target for investigating disease aetiology. Sequence specific primer polymerase chain reaction with allele sequencing was used to determine HLA-DQA1 and DQB1 allele frequencies (AF) for 165 KD patients and 119 healthy controls of black Jamaican Afro-Caribbean origin. HLA class I alleles A*01, A*03, A*25, B*07 and Cw*08:02, previously identified as KD associated in a different ethnicity, were also analysed. Allele sequencing confirmed typing accuracy but no statistically significant differences in AF were identified between KD patients and controls. Furthermore, KD subgroups including patient gender, family history and multiple- or single-site scarring did not show significant allele-disease associations.

The efficacy of a cognitively orientated carers group in an early intervention in psychosis service--a pilot study.

A significant amount of evidence has demonstrated that families and carers play an important role in an individual's recovery from a first episode of psychosis (FEP) and can significantly reduce relapse rates. This, in addition to the fact that caring for an individual experiencing their FEP can be incredibly stressful, suggests that the development of appropriate support for carers must be an integral part of any Early Intervention in Psychosis Service (EIPS). This study examines the efficacy of a closed structured group designed for carers of individuals experiencing their FEP based in Southampton city. A 12-session cognitively orientated group programme covering a range of areas was attended by 18 carers over a 6-month period. Following the group, a significant decrease was found in the carer's negative appraisals of the impact of psychosis, feelings of burden, depression and anxiety rates as measured by the Experience of Caregiving Inventory (ECI), Caregiver Burden Inventory (CBI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). A significant positive correlation was also found between carer's negative appraisals and their anxiety and depression rates, although further research is needed to clarify the causality of this relationship.

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Localisation of a novel region of recurrent amplification in follicular lymphoma to an approximately 6.8 Mb region of 13q32-33.

Follicular lymphoma (FL) is characterised by the presence of the t(14;18)(q32;q21) and represents approximately 25% of new cases of non-Hodgkin's lymphoma. While the t(14;18) is a well-documented rearrangement, the role of secondary cytogenetic abnormalities in the development and progression of these tumours remains unclear. Comparative genomic hybridisation was used to characterise changes in DNA copy number in tumour DNA from patients with this malignancy. The mean numbers of deletion and amplification events found in each of the 45 samples studied were 1.8 and 2.3, respectively. Regions of recurrent (>10% tumour samples) gain involved chromosomes 2p13-16 (16%), 7 (20%), 12 (16%), 13q21-33 (18%), 18 (27%), and X (36%) and frequent losses localised to 6q (29%) and 17p (20%). Amplification of chromosome 13 represents a novel finding in FL. The minimal amplified region was refined to a 6.8-Mb interval of 13q32-33 between the BAC clones 88K16 and 44H20 by fluorescence in situ hybridisation studies using metaphase chromosomes derived from tumour material. There are a number of reports in the literature suggesting that amplification of chromosome 13 also occurs in other human cancers. The location of the putative oncogene on 13q described here in follicular and transformed lymphoma may also be important in the evolution of many other malignancies.

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Kabuki syndrome-like features in monozygotic twin boys with a pseudodicentric chromosome 13.

We present monozygotic twin boys with features of Kabuki syndrome. The twins were discordant for cleft palate and coarctation of the aorta. The occurrence of Kabuki syndrome in monozygotic twins has not been previously reported and reinforces the belief that this condition has a genetic basis. Chromosomal analysis on the boys showed a pseudodicentric chromosome 13 with an inactive centromere and satellite stalks at 13q12.11: 46,XY,psu dic(13)(13pter-->13q12.11::13p12-->13q11.00:: 13q12.11-->13qter). Their phenotypically normal mother appears to carry the same pseudodicentric chromosome 13.

Evaluation of a psychophysiological model of classical fear conditioning in anxious patients.

Skin conductance variables have been compared in 30 anxious patients and 30 controls to investigate the extent to which anxiety is associated with increased autonomic arousal, reduced habituation or enhanced aversive conditioning. Skin conductance level, variability (spontaneous fluctuations) and response amplitudes to tones were significantly greater in patients than controls. Habituation of skin conductance responses to a series of ten innocuous tones (80 dB, 1 s) did not differ between the groups. Aversively conditioned skin conductance responses were measured to a further series of ten tones after a conditioning trial in which a loud white noise (100 dB) followed tone 11. All subjects showed enhanced (conditioned) responses to the tones after the conditioning trial, but patients did not show greater conditioning than controls. The results indicate that anxious neurotic out-patients have greater sweat gland activity and reactivity than controls but fail to demonstrate differences in central mechanisms of habituation or conditioning.