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S Milne

Publications and source records attributed to S Milne.

At least 37 records · Page 2Linked to original sources
PubMed2000

Construction of a high-resolution 2.5-Mb transcript map of the human 6p21.2-6p21.3 region immediately centromeric of the major histocompatibility complex.

We have constructed a 2.5-Mb physical and transcription map that spans the human 6p21.2-6p21.3 region and includes the centromeric end of the MHC, using a combination of techniques. In total 88 transcription units including exons, cDNAs, and cDNA contigs were characterized and 60 were confidently positioned on the physical map. These include a number of genes encoding nuclear and splicing factors (Ndr kinase, HSU09564, HSRP20); cell cycle, DNA packaging, and apoptosis related [p21, HMGI(Y), BAK]; immune response (CSBP, SAPK4); transcription activators and zinc finger-containing genes (TEF-5, ZNF76); embryogenesis related (Csa-19); cell signaling (DIPP); structural (HSET), and other genes (TULP1, HSPRARD, DEF-6, EO6811, cyclophilin), as well as a number of RP genes and pseudogenes (RPS10, RPS12-like, RPL12-like, RPL35-like). Furthermore, several novel genes (a Br140-like, a G2S-like, a FBN2-like, a ZNF-like, and B1/KIAA0229) have been identified, as well as cDNAs and cDNA contigs. The detailed map of the gene content of this chromosomal segment provides a number of candidate genes, which may be involved in several biological processes that have been associated with this region, such as spermatogenesis, development, embryogenesis, and neoplasia. The data provide useful tools for synteny studies between mice and humans, for genome structure analysis, gene density comparisons, and studies of nucleotide composition, of different isochores and Giemsa light and Giemsa dark bands.

Amino Acid Sequence↗
PubMed1999

The chicken B locus is a minimal essential major histocompatibility complex.

Here we report the sequence of the region that determines rapid allograft rejection in chickens, the chicken major histocompatibility complex (MHC). This 92-kilobase region of the B locus contains only 19 genes, making the chicken MHC roughly 20-fold smaller than the human MHC. Virtually all the genes have counterparts in the human MHC, defining a minimal essential set of MHC genes conserved over 200 million years of divergence between birds and mammals. They are organized differently, with the class III region genes located outside the class II and class I region genes. The absence of proteasome genes is unexpected and might explain unusual peptide-binding specificities of chicken class I molecules. The presence of putative natural killer receptor gene(s) is unprecedented and might explain the importance of the B locus in the response to the herpes virus responsible for Marek's diseases. The small size and simplicity of the chicken MHC allows co-evolution of genes as haplotypes over considerable periods of time, and makes it possible to study the striking MHC-determined pathogen-specific disease resistance at the molecular level.

Amino Acid Sequence↗
PubMed1999

Gene organisation determines evolution of function in the chicken MHC.

Some years ago, we used our data for class I genes, proteins and peptide-binding specificities to develop the hypothesis that the chicken B-F/B-L region represents a "minimal essential MHC". In this view, the B locus contains the classical (highly expressed and polymorphic) class I alpha and class II beta multigene families, which are reduced to one or two members, with many other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immune response to certain infectious pathogens, due to peptide-binding specificity and cell-surface expression level. This stands in stark contrast to well-studied mammals like humans and mice, in which every haplotype is more-or-less responsive to every pathogen and vaccine, presumably due to the multigene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion of the B complex and examined the location and polymorphism of the class I (B-F) alpha, TAP and class II (B-L) beta genes. The region is remarkably compact and simple, with many of the genes expected from the MHC of mammals absent, including LMP, class II alpha and DO genes as well as most class III region genes. However, unexpected genes were present, including tapasin and putative natural killer receptor genes. The region is also organised differently from mammals, with the TAPs in between the class I genes, the tapasin gene in between the class II (B-L) beta genes, and the C4 gene outside of the class I alpha and class II beta genes. The close proximity of TAP and class I alpha genes leads to the possibility of co-evolution, which can drive the use of a single dominantly expressed class I molecule with peptide-binding specificity like the TAP molecule. There is also a single dominantly expressed class II beta gene, but the reason for this is not yet clear. Finally, the presence of the C4 gene outside of the classical class I alpha and class II beta genes suggests the possibility that this organisation was ancestral, although a number of models of organisation and evolution are still possible, given the presence of the Rfp-Y region with non-classical class I alpha and class II beta genes as well as the presence of multigene families of B-G and rRNA genes.

Animals↗
PubMed1998

Large-scale sequence comparisons reveal unusually high levels of variation in the HLA-DQB1 locus in the class II region of the human MHC.

Comparison of genomic sequences flanking the HLA-DQB1 locus in the human MHC class II region reveals local sequence variation of up to 10%, which is the highest level of sequence variation found in the human genome so far. The variation is haplotype-specific and extends far beyond the transcriptional unit of the DQB1 gene, suggesting hitch-hiking along with functionally selected alleles as the most likely mechanism. All major insertions/deletions (indels) were found to be of retroviral origin and in the immediate upstream region of DQB1. Possible cis-acting effects of these indels on the transcriptional regulation of DQB1 are discussed.

Ataxin-1↗
PubMed1998

A retrospective epidemiological analysis of non-accidental head injury in children in Scotland over a 15 year period.

A retrospective analysis of the epidemiological characteristics of non-accidental head injury (NAHI) in children in Scotland over the last fifteen years from 1981 until March 1996 was performed. The information was provided by the Information and Statistics Division of the Scottish Health Service. The average incidence of NAHI calculated over this period was 0.04 cases per year per 1000 children under 5 years. Fifty-five per cent of all cases occurred in those children who were less than a year old. 41% of cases were inflicted by a parent but in 47% the perpetrator could not be identified. The mortality rate was found to be 2%. Non-accidental head injury cases identified using the ICD-9 coding classification system gives a surprisingly low incidence. This number is probably an underestimate and the reasons for this are discussed. A prospective epidemiological analysis of NAHI in children in Scotland is being undertaken to determine the true incidence.

Adolescent↗
PubMed1998

The natural decomposition of adipocere.

Adipocere is a waxy substance which sometimes forms from the adipose tissue of dead bodies, especially when they are under water. A disinterment in southern Ontario lead to the recovery of extensive adipocere from an interment which occurred in AD 1869. Subsequent laboratory research was designed to explore the conditions under which adipocere will disappear, the goal being to identify strategies for estimating a range of time since death in cases where adipocere is present. Varieties of aerobic or facultatively anaerobic microorganisms from the surface of the adipocere were separated and identified. In culture, the gram positive bacteria were able to degrade the adipocere. We propose that the persistence of adipocere is related to the exclusion of gram positive bacteria from the burial environment. The role of bacteria in adipocere formation and degradation must be understood before we can use the presence of adipocere to extrapolate information about the post-death interval.

Adipose Tissue↗
PubMed1997

The chromosome 6 sequencing project at the Sanger Centre.

Chromosome 6 is probably best known for encoding the major histocompatibility complex (MHC) which is essential to the human immune response. In addition, it has been shown to be associated with many diseases such Schizophrenia, Diabetes, Arthritis, Haemochromatosis, Narcolepsy, Epilepsy, Retinitis Pigmentosa, Deafness, Ovarian Cancer, and many more. Chromosome 6 is about 180 Mb in size and is estimated to encode around 3500 genes of which only about 10% are currently known. It is our aim to map, sequence and annotate the entire chromosome in close collaboration with the chromosome 6 community.

Chromosomes, Human, Pair 6↗
PubMed1995

Sex differences in patients admitted to a regional secure unit.

The case notes of all admissions to a Regional Secure Unit over a 12-year period were examined. A higher proportion of females had a diagnosis of personality disorder. Women were less likely to have a prosecuted offence associated with admission but were more likely to be charged with fire-setting. Patients with personality disorder were more likely to be transferred to special hospitals. Women were nearly three times as likely as men to be transferred to maximum security and this was not accounted for by the excess of females with personality disorder. There was net movement of men out of special hospitals whereas the opposite was true for women. Possible explanations for this are discussed.

Adolescent↗
PubMed1995

Physical morbidity in patients admitted to a private hospital for detoxification from alcohol.

A survey of patients admitted to a private hospital for detoxification from alcohol found similar levels of physical morbidity and withdrawal complications to a group admitted to a National Health Service alcohol treatment unit. Although private patients tended to be older than National Health Service patients, the two groups were similar on a number of other variables. The implications for those involved in the management of patients who abuse alcohol are discussed.

Adult↗
PubMed1994

Long-term outcome of post-partum psychiatric illness requiring admission.

Among 65 women admitted to a mother and baby unit within 6 months post-partum, 53 were followed up for an average of 8.8 years. Women who had no previous history of psychiatric illness or who had experienced previous puerperal illness only, did significantly better at follow-up. The majority of these women had presented with a clinical picture of major depression. Past psychiatric history is confirmed as an important prognostic indicator in post-partum illnesses.

Adolescent↗
PubMed1994

Suicide in Scotland 1988-1989. Psychiatric and physical morbidity according to primary care case notes.

BACKGROUND: The aim was to identify the amount of psychiatric and physical morbidity identified in suicide victims prior to death. METHOD: A survey was made of primary care records of Scottish suicide victims in the years 1988 and 1989. RESULTS: Less morbidity was encountered than in previous studies. Single persons and persons from lower socio-economic groups were less likely to have a diagnosis of depression. No association was found between physical and psychiatric morbidity. Depressed single persons and depressed persons from lower socio-economic groups were less likely to receive antidepressants. GPs prescribed lower dosages of antidepressants than psychiatrists. Patients receiving antidepressants were more likely to die by drug overdose. CONCLUSIONS: There are groups in whom depression may be being overlooked and others in whom depression could be treated more vigorously. There are risks in prescribing antidepressants which are potentially fatal in overdose.

Alcoholism↗
PubMed1994

Role of doctors in the prevention of suicide: the final consultation.

BACKGROUND: It is generally assumed that people committing suicide see their doctor shortly before their death, and consequently that enhancing doctors' psychiatric knowledge and interview skills might help prevent some suicides. AIM: A study was undertaken to determine the nature and timing of final contacts with medical practitioners by people committing suicide. METHOD: Adults dying by suicide in Scotland during 1988-89 were identified by the General Register Office for Scotland and their primary care case notes studied. RESULTS: Within this national sample, medical contact near to the time of the suicidal act was rare, except for those individuals who had a previous psychiatric history. CONCLUSION: These data suggest that medical practitioners, particularly those working in primary care, are not failing to detect and intervene in significant numbers of preventable suicides. Consequently, the likelihood of implementing successful suicide prevention strategies based within primary care is open to question. Greater awareness of the risk of eventual suicide in those with a previous history of psychiatric disorder may contribute to any future reduction in suicide rates.

Adolescent↗
PubMed1993

Porphyrin induced calcium release from skeletal muscle sarcoplasmic reticulum.

Micromolar concentrations of the porphyrin mesotetra(4-N-methylpyridyl)porphine tetraiodide is shown to induce rapid release of Ca2+ from skeletal muscle sarcoplasmic reticulum vesicles. Porphyrin-induced Ca2+ release is stimulated by ATP (KdATP = 100 microM) and Ca2+ (KdCa = 1 microM) and is inhibited by Mg2+ (KI = 220 microM) and ruthenium red (KI = 7 nM). The porphyrin is also shown to stimulate high affinity [3H]ryanodine binding by decreasing the dissociation constant (kd) and increasing the binding capacity (Bmax). Moreover, in the presence of Mg2+, receptor binding is sensitized to activation by Ca2+, and porphyrin-stimulated channel activity is sensitized to activation by Ca2+. These observations show that porphyrin-induced Ca2+ release is due to a direct interaction with the Ca2+ release protein from sarcoplasmic reticulum.

Adenosine Triphosphate↗