Biomedical subjects
Publications and source records attributed to S J O'Brien.
Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types.
The cheetah is unusual among fields in exhibiting near genetic uniformity at a variety of loci previously screened to measure population genetic diversity. It has been hypothesized that a demographic crash or population bottleneck in the recent history of the species is causal to the observed monomorphic profiles for nuclear coding loci. The timing of a bottleneck is difficult to assess, but certain aspects of the cheetah's natural history suggest it may have occurred near the end of the last ice age (late Pleistocene, approximately 10,000 years ago), when a remarkable extinction of large vertebrates occurred on several continents. To further define the timing of such a bottleneck, the character of genetic diversity for two rapidly evolving DNA sequences, mitochondrial DNA and hypervariable minisatellite loci, was examined. Moderate levels of genetic diversity were observed for both of these indices in surveys of two cheetah subspecies, one from South Africa and one from East Africa. Back calculation from the extent of accumulation of DNA diversity based on observed mutation rates for VNTR (variable number of tandem repeats) loci and mitochondrial DNA supports a hypothesis of an ancient Pleistocene bottleneck that rendered the cheetah depauperate in genetic variation for nuclear coding loci but would allow sufficient time for partial reconstitution of more rapidly evolving genomic DNA segments.
Feline leukemia viruses carrying transduced v-myc genes (myc-FeLV) induce tumors of clonal origin, suggesting that activated myc alone is not sufficient for tumorigenesis. To investigate the hypothesis that insertional mutagenesis plays a role by activating genes which collaborate with v-myc, we looked for evidence of common proviral integration sites in these tumors. By inverse polymerase chain reaction we identified a 6-kb domain, designated fit-1, in which FeLV proviruses were inserted in four of nine (44%) T-cell tumors induced by myc-FeLV. The fit-1 locus was mapped to feline chromosome B2 and appears to be distinct from known oncogenes located on this chromosome. Fit-1 represents a novel common proviral integration region which may harbor a cellular gene which acts in concert with the myc gene in T-cell tumorigenesis.
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In order to describe hospital bed usage by people with HIV disease in a provincial setting, a retrospective analysis of admissions to hospital wards in Oxford was undertaken for people admitted to hospital with all HIV-related illnesses or complications of HIV-related treatment. A total of 83 people were identified as having been admitted to hospital between January 1986 and the end of August 1990. Average length of hospital stay, the number of admissions per observed person-year and the in-patient days per observed person-year decreased. Of the 2,446 days spent in hospital, 913 were by people with an AIDS diagnosis; 1,533 days were spent by people who did not fulfil the World Health Organisation/Centers for Disease Control (WHO/CDC) classification for AIDS but who were admitted because of their HIV disease. AIDS is an end-point of infection with HIV. Pre-AIDS morbidity, a spectrum of illness of increasing severity from minor illness up to the point of WHO/CDC level AIDS, is a major determinant of hospital care and has previously been underestimated. In order to calculate the best estimates of hospital care needed, HIV disease should be regarded as a single entity and the artificial barrier dividing HIV illnesses from AIDS should be discarded.
Recent advances in gene mapping technologies have led to increased emphasis in developing representative genetic maps for several species, particularly domestic plants and animals. These maps are being compiled with two distinct goals: to provide a resource for genetic analysis, and to help dissect the evolution of genome organization by comparing linkage relationships of homologous genes. We propose here a list of 321 reference anchor loci suitable for comparative gene mapping in mammals and other vertebrate classes. We selected cloned mouse and human functional genes spaced an average of 5-10 centiMorgans throughout their respective genomes. We also attempted to include loci that are evolutionarily conserved and represented in comparative gene maps in other mammalian orders, particularly cattle and the domestic cat. We believe that the map may provide the basis for a unified approach to comparative analysis of mammalian species genomes.
The purpose of this study was to compare computed tomographic (CT) arthrography with arthroscopy in the evaluation of patients with anterior knee pain. The authors studied 23 patients with patellar plicae at CT arthrography. Twenty of 21 patients presumed to have medial plicae at arthroscopy had similar findings at CT arthrography (sensitivity, 95%; specificity, 100%). However, 10 of 12 suprapatellar plicae and 11 of 11 lateral plicae seen at CT arthrography were not seen at arthroscopy. All 11 patients with a diagnosis of no or mild chondromalacia patellae at arthroscopy had similar CT arthrographic findings, whereas seven of 11 patients presumed to have moderate or severe chondromalacia patellae at arthroscopy had matching CT arthrographic results (sensitivity, 100%; specificity, 73%). CT arthrography was much more accurate in classifying plicae as thick (66%) as opposed to classifying plicae as thin (17%). The authors conclude that CT arthrography is an accurate and specific modality for distinguishing patients with anterior knee pain due to plicae from those with anterior knee pain due to differing causes.
Injury to the metatarsophalangeal (MP) joint of the great toe, often termed "turf-toe", is a common occurrence in football. We have identified four cases of first MP plantar capsular injury with diastasis of a bipartite sesamoid. In three cases, observation and protection resulted in progressive widening of the fragments associated with pain and disability. These players required resection of the distal sesamoid fragment and repair of the volar capsule. The fourth player underwent acute repair of the medial retinaculum and capsule. All players have had a full return to sports activity. Diastasis of components of a partite sesamoid provides objective evidence of disruption of the plantar capsular mechanism. Early recognition of this condition confirmed by stress radiographs is recommended. Treatment may include early protection followed by resection, if painful, or acute repair of the retinaculum. Previous descriptions of turf-toe have not included injuries to the sesamoid complex of the first MP joint. In our opinion, the term turf-toe should represent the consequences of a hyperextension injury to the first MP joint in which the volar capsule has been disrupted proximal to the sesamoid. A classification for first MP joint injuries is presented.
Alterations of the p53 tumor suppressor gene have been observed in a variety of human and mouse tumors. For investigation of the role of this gene in tumors in cats, feline p53 cDNA was molecularly cloned by PCR amplifications using primers based on the sequences conserved among several species. The cloned cDNA appeared to cover approximately 90% of the open reading frame of the feline p53 gene and had characteristic structures in common with the p53 genes of several other species. The amino acid sequence similarities of the feline p53 with the human, mouse, rat and chicken counterparts were 82.9%, 75.6%, 76.5% and 57.2% respectively. Moreover, using a panel of feline x rodent somatic cell hybrids, the feline p53 gene was assigned to feline chromosome E1. These data will be useful for determining the role of the p53 tumor suppressor gene in feline tumors.
Pituitary responses to gonadotrophin-releasing hormone (GnRH) and prolactin and steroid secretory profiles were examined in two populations of adult, female lions in the Serengeti (one outbred in the Serengeti Plains and one inbred in the Ngorongoro Crater) to determine whether reductions in genetic variability adversely affected endocrine function. GnRH-induced gonadotrophin secretion was also examined after adrenocorticotrophic hormone (ACTH) treatment to determine whether acute increases in serum cortisol altered pituitary function. Anaesthetized lions were administered (i) saline i.v. after 10 and 100 min of blood sampling, (ii) saline at 10 min and GnRH (1 micrograms kg-1 body weight) after 100 min; or (iii) ACTH (3 micrograms kg-1) at 10 min and GnRH after 100 min of sampling. Basal serum cortisol and basal and GnRH-induced gonadotrophin secretion were similar (P > 0.05) between females of the Ngorongoro Crater and Serengeti Plains. After ACTH, serum cortisol increased two- to threefold over baseline values and the response was unaffected (P > 0.05) by location. ACTH-induced increases in serum cortisol had no effect on subsequent basal or GnRH-stimulated luteinizing hormone (LH) or follicle-stimulating hormone (FSH) secretion. Overall mean serum progesterone concentrations ranged from 0.2 to 5.4 ng ml-1 with the exception of four females (two in the Serengeti and two in the Crater; progesterone range, 18.4-46.5 ng ml-1) that were presumed pregnant (three of these females were observed nursing cubs several weeks later).(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-six domestic cats received 100 iu hCG (i.m.) on day 1, 2 or 3 of a natural, behavioural oestrus. Twenty-two anoestrous cats were injected with 150 iu pregnant mares' serum gonadotrophin (PMSG; i.m.) followed 84 h later by 100 iu hCG. Twenty-four to 26 h after hCG, all cats were examined laparoscopically to determine the number of ovarian follicles and to recover follicular eggs. Mature eggs were cultured with conspecific spermatozoa and examined 30 h later for cleavage. Within the natural oestrus group, cats on day 1 produced fewer (P < 0.05) follicles and total eggs than females on day 2 or 3, and 88.9% of the day 1 eggs were degenerate or immature and unsuitable for in vitro fertilization (IVF). Although only 54.5% of the cats in the PMSG/hCG group exhibited overt oestrus, mean (+/- SEM) numbers of follicles (9.7 +/- 0.8) and oocytes recovered (8.7 +/- 0.8) were at least twofold greater (P < 0.001) than those measured in the natural oestrus group (3.7 +/- 0.6; 3.4 +/- 0.6, respectively) or subgroups on day 2 (3.7 +/- 0.4; 3.3 +/- 0.4) and day 3 (5.7 +/- 0.8; 5.3 +/- 0.8). Overall, the proportion of eggs cleaving in vitro was similar (P > 0.05) between the natural oestrus group (48.3%) and the PMSG/hCG group (50.9%), but the latter group produced more than twice the number of embryos per donor. Embryo quality was unaffected (P > 0.05) by day of hormone treatment, and more than 80% of all two-cell embryos were rated good-to-excellent quality.(ABSTRACT TRUNCATED AT 250 WORDS)
Based on anatomic and surgical dissections, the anatomy of the shoulder region is described in terms of four layers that overlie and support the glenohumeral joint. Each layer envelops the glenohumeral joint on its anterior, lateral, and posterior aspects, and between each layer there is a plane for safe and easy dissection. Layer 1 is composed of the deltoid and pectoralis major muscle bellies with their overlying fascia and enveloping epimysium. Anteriorly, Layer 2 consists of the clavipectoral fascia, the conjoined tendon of the short head of the biceps and coracobrachialis, and the coracoacromial ligament. Posteriorly, Layer 2 is the dense posterior scapular fascia that overlies the infraspinatus and teres minor muscle bellies. It is continuous with the clavipectoral fascia around the lateral aspect of the proximal humerus. Deep to Layer 2, the subdeltoid bursa yields a dissection plane that encompasses the anterior, lateral, superior, and variably the posterior aspects of the glenohumeral joint. Layer 3 consists of the deep layer of the subdeltoid bursa and the underlying musculotendinous units of the rotator cuff, including subscapularis, supraspinatus, infraspinatus, and teres minor. Layer 4 is the capsule of the glenohumeral joint. This includes the glenohumeral ligaments and coracohumeral ligament. These four layers were present and consistent in each shoulder dissected. Significant variations were present only within the deepest layer (shoulder joint capsule). This system can serve as a learning tool and will provide a more organized approach to facilitate surgical dissection in the region.
A method for the successful extraction of sequestered cellular DNA from 14,000-year-old fossil bones was developed and applied to asphalt-preserved specimens of the extinct saber-toothed cat, Smilodon fatalis. Two distinct gene segments, the mitochondrial gene for 12S rRNA and nuclear FLA-I (the feline class I major histocompatibility complex gene), from three different individual fossil specimens were cloned and sequenced after PCR amplification. Comparison of fossil-derived DNA sequences to homologous regions in 15 living carnivorous species, including 9 species of Felidae and 6 nonfelids, affirmed the phylogenetic placement of Smilodon within the modern radiation of Felidae distinct from the Miocene paleofelid (Nimravidae) saber-toothed "cat" species. These results raise the prospect of obtaining genetically informative DNA from preserved bones of extinct fossil species, particularly among the 2 million specimens excavated from the asphaltic sediments at Rancho La Brea in metropolitan Los Angeles.
The structural gene for human keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, consists of three coding exons and two introns typical of other fibroblast growth factor loci. A portion of the KGF gene, located on chromosome 15, is amplified to approximately 16 copies in the human genome, and these highly related copies (which consist of exon 2, exon 3, the intron between them, and a 3' noncoding segment of the KGF transcript) are dispersed to multiple human chromosomes. The KGF-like sequences are transcriptionally active, differentially regulated in various tissues, and composed of three distinct classes of coding sequences that are 5% divergent from each other and from the authentic KGF sequence. Multiple copies of KGF-like genes were also discovered in the genomic DNAs of chimpanzee and gorilla but were not found in lesser apes (gibbon), Old World monkeys (African green monkey and macaques), mice, or chickens. The pattern of evolutionary occurrence suggests that a primordial KGF gene was amplified and chromosomally dispersed subsequent to the divergence of orangutan from African apes but before the trichotomous divergence of human, chimpanzee, and gorilla 5-8 million years ago. The appearance of a transcriptionally active and chromosomally dispersed multigene KGF family may have implications in the evolution of the great apes and humans.
This study evaluated the cellular repopulation of deep-frozen meniscal autografts. Medial menisci of adult dogs were excised, deep-frozen in liquid nitrogen (-196 degrees C) for 10 min, and orthotopically reimplanted into the joint. Deep-freezing was found to effectively kill all the cells within the meniscus as determined by the absence of Na(2)35SO4 incorporation. Following orthotopic replacement within the knee joint, menisci were repopulated with cells that seemed to originate from the adjacent synovium. These cells migrated over the surface of the meniscus and began to invade the deeper layers of the tissue. However, even after 6 months, the central core of the meniscus remained acellular. While the new cells appeared to modulate into cells that are similar in appearance to meniscal fibrochondrocytes, the exact phenotypic expression of these newly differentiated cells has yet to be determined. Histological alterations, as manifested by a loss of normal orientation of the collagen architecture of the superficial layers of the meniscus; was evident at 6 months and suggests that a remodeling phenomenon may be associated with the cellular repopulation. While biomaterial studies have not been carried out on these specimens, the morphologic alterations observed in the collagen orientation would suggest a possible alteration in the material properties of the repopulated meniscus. The clinical implication of this study is that the structural remodeling associated with the cellular repopulation of deep-frozen meniscal allografts may make the transplanted meniscus more susceptible to injury.
We have developed a sensitive technique for detecting single base substitutions in polymerase chain reaction (PCR) products from individuals heterozygous for polymorphisms or new mutations. This technique takes advantage of the formation of heteroduplexes in the PCR between different alleles from heterozygous individuals. These heteroduplexes can be detected on polyacrylamide gels because they migrate slower than their corresponding homoduplexes. Using PCR, we have generated a series of point mutations in a defined region of DNA in the equine infectious anemia virus (EIAV). Each mutation is the result of a single base substitution. By mixing the PCR products amplified from these mutations with one another, as well as with wildtype PCR products, we can generate heteroduplexes in which the identity of the mismatched bases is known. We detected eight of nine point mutations using this technique. We have also modified the electrophoretic conditions to optimize the detection of these heteroduplexes. In addition, the usefulness of this technique is demonstrated by its ability to detect a mutation in the cystic fibrosis gene that is the result of a single base substitution. This technique should prove useful for rapidly screening large numbers of individuals for new mutations or polymorphisms.