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Stephen J O'Brien

Publications and source records attributed to Stephen J O'Brien.

At least 91 records · Page 5Linked to original sources
PubMed2003

Reconstructing the genomic architecture of mammalian ancestors using multispecies comparative maps.

Rapidly developing comparative gene maps in selected mammal species are providing an opportunity to reconstruct the genomic architecture of mammalian ancestors and study rearrangements that transformed this ancestral genome into existing mammalian genomes. Here, the recently developed Multiple Genome Rearrangement (MGR) algorithm is applied to human, mouse, cat and cattle comparative maps (with 311-470 shared markers) to impute the ancestral mammalian genome. Reconstructed ancestors consist of 70-100 conserved segments shared across the genomes that have been exchanged by rearrangement events along the ordinal lineages leading to modern species genomes. Genomic distances between species, dominated by inversions (reversals) and translocations, are presented in a first multispecies attempt using ordered mapping data to reconstruct the evolutionary exchanges that preceded modern placental mammal genomes.

Algorithms↗
PubMed2003

Traumatic posterior hip subluxation in American football.

BACKGROUND: Traumatic posterior hip subluxation is a potentially devastating injury that is often misdiagnosed as a simple hip sprain or strain. The purpose of the present study was to outline the injury mechanism, pathoanatomy, clinical and radiographic findings, and treatment of traumatic hip subluxation in an athletic population. METHODS: Over a nine-year period, eight participants in American football who had sustained a traumatic posterior hip subluxation were evaluated and treated. The injury mechanism, clinical findings, and radiographic findings were reviewed. The mean duration of follow-up was thirty-four months. RESULTS: The most common mechanism of injury was a fall on a flexed, adducted hip. Physical examination revealed painful limitation of hip motion. Initial radiographs demonstrated a characteristic posterior acetabular lip fracture. Initial magnetic resonance images revealed disruption of the iliofemoral ligament, hemarthrosis, and a viable femoral head. Two players were treated acutely with hip aspiration, and all eight players were treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Six players recovered and returned to the previous level of competition. Two players had development of severe osteonecrosis and ultimately required total hip arthroplasty. CONCLUSION: The pathognomonic radiographic and magnetic resonance imaging triad of posterior acetabular lip fracture, iliofemoral ligament disruption, and hemarthrosis defines traumatic posterior hip subluxation. Patients in whom large hemarthroses are diagnosed on magnetic resonance images should undergo acute aspiration, and all players should be treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Patients who have no sign of osteonecrosis on magnetic resonance imaging at six weeks can safely return to sports activity. Patients in whom osteonecrosis is diagnosed at six weeks are at risk for collapse and joint degeneration, and they should be advised against returning to sports.

Accidental Falls↗
PubMed2003

Quantitative polymerase chain reaction-based assay for estimating DNA yield extracted from domestic cat specimens.

A quantitative polymerase chain reaction (PCR) assay has been developed for the quantification of genomic DNA extracted from domestic cat samples. The assay, which targets highly repetitive genomic short interspersed nuclear elements (SINE), can be performed rapidly and is highly sensitive, detecting as little as 10 fg of feline genomic DNA. The assay was linear over a 10(6) dilution range. We have recently developed a short tandem repeat (STR) multiplex panel for forensic analysis of feline specimens. The SINE assay is an integral part of the forensic typing system. The sensitivity of the assay will enable forensic examiners to determine the likelihood of success of genotyping sample extracts with the STR panel without sacrificing valuable DNA necessary to perform genotyping of samples.

Animals↗
PubMed2003

[Paternity assignment of giant panda by microsatellite genotyping].

We used genotype data across 18 microsatellite loci to establish the paternity of giant panda cubs at the Chengdu Zoo and the Chengdu Research Base of Giant Panda Breeding. The results demonstrate that the combined exclusion probability using these 18 microsatellite loci is 0.999921 while confidence is 95 % when the mother is known; if mother is unknown then the exclusion probability is 0.994109, but the confidence of this is less than 80%. Since the mother-offspring relationship is known in captive populations, the results could resolve unknown paternities in the Chengdu ex situ populations. However, to establish accurately the genetic relationships of wild giant pandas,more microsatellite loci may be required.

English Abstract↗
PubMed2002

Feline immunodeficiency virus integration in B-cell lymphoma identifies a candidate tumor suppressor gene on human chromosome 15q15.

Infection with immunosuppressive lentiviruses is associated with increased cancer risk,but most studies have implicated indirect mechanisms as the tumor cells generally lack integrated viral sequences. An exception wasfound in a B-cell lymphoma (Q254) where the tumor cells contained a single integrated feline immunodeficiency virus genome. Additional analysis now indicates that feline immunodeficiency virus integration in lymphoma Q254 resulted in promoter insertion and truncation of a conserved gene on feline chromosome B3, whereas the unaffected allele of the gene appeared to be transcriptionally down-regulated. The orthologous human gene (FLJ12973), is expressed ubiquitously and encodes a WD-repeat protein with structural similarity to DDB2, the small subunit of the xeroderma pigmentosum XP-E complex. Moreover, the gene is located within a region of frequent tumor-specific deletions on chromosome 15q15. These observations demonstrate the direct mutagenic potential of the lentiviruses and identify a new candidate tumor suppressor gene.

Amino Acid Sequence↗
PubMed2002

Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS.

Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Modulating influence on HIV/AIDS by interacting RANTES gene variants.

RANTES (regulated on activation normal T cell expressed and secreted), a ligand for the CC chemokine receptor 5, potently inhibits HIV-1 replication in vitro. We tested the influence of four RANTES single nucleotide polymorphism (SNP) variants and their haplotypes on HIV-1 infection and AIDS progression in five AIDS cohorts. Three SNPs in the RANTES gene region on chromosome 17 (403A in the promoter, In1.1C in the first intron, and 3'222C in the 3' untranslated region) are associated with increased frequency of HIV-1 infection. The common In1.1C SNP allele is nested within an intronic regulatory sequence element that exhibits differential allele binding to nuclear proteins and a down-regulation of gene transcription. The In1.1C allele or haplotypes that include In1.1C display a strong dominant association with rapid progression to AIDS among HIV-1-infected individuals in African-American, European-American, and combined cohorts. The principal RANTES SNP genetic influence on AIDS progression derives from the down-regulating RANTES In1.1C allele, although linkage disequilibrium with adjoining RANTES SNPs including a weaker up-regulating RANTES promoter allele (-28G), can modify the observed epidemiological patterns. The In1.1C-bearing genotypes account for 37% of the attributable risk for rapid progression among African Americans and may also be an important influence on AIDS progression in Africa. The diminished transcription of RANTES afforded by the In1.1C regulatory allele is consistent with increased HIV-1 spread in vivo, leading to accelerated progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2002

The Feline Genome Project.

The compilation of a dense gene map and eventually a whole genome sequence (WGS) of the domestic cat holds considerable value for human genome annotation, for veterinary medicine, and for insight into the evolution of genome organization among mammals. Human association and veterinary studies of the cat, its domestic breeds, and its charismatic wild relatives of the family Felidae have rendered the species a powerful model for human hereditary diseases, for infectious disease agents, for adaptive evolutionary divergence, for conservation genetics, and for forensic applications. Here we review the advantages, rationale, and present strategy of a feline genome project, and we describe the disease models, comparative genomics, and biological applications posed by the full resolution of the cat's genome.

Animals↗
PubMed2002

Balanced polymorphism selected by genetic versus infectious human disease.

The polymorphisms within the human genome include several functional variants that cause debilitating inherited diseases. An elevated frequency of some of these deleterious mutations can be explained by a beneficial effect that confers a selective advantage owing to disease resistance in carriers of such mutations during an infectious disease outbreak. We here review plausible examples of balanced functional polymorphisms and their roles in the defense against pathogens. The genome organization of the chemokine receptor and HLA gene clusters and their influence on the HIV/AIDS epidemic provides compelling evidence for the interaction of infectious and genetic diseases in recent human history.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Nonpathogenic lion and puma lentiviruses impart resistance to superinfection by virulent feline immunodeficiency virus.

Lion lentivirus (LLV) and puma lentivirus (PLV) exist as highly divergent virus clades among populations of indigenously infected nondomestic Felidae. The feline immunodeficiency virus (FIV) is highly divergent from LLV and PLV and is pathogenic for domestic cats. When domestic cats are infected with LLV or PLV, they have immunologically and clinically silent persistent infections. We examined whether LLV or PLV infection might impart resistance to FIV superinfection in vitro by infecting domestic cat lymphoid cells with PLV and assessing resistance of these cells to FIV. We found that infection with FIV was highly restricted by prior established PLV infection. To examine whether this resistance applied in vivo, domestic cats were asymptomatically infected with either LLV or PLV and then challenged with pathogenic FIV. Although all cats became infected with FIV, prior LLV or PLV exposure blunted CD4 + cell depletion and suppressed plasma and peripheral blood mononuclear cell FIV loads relative to FIV-challenged controls not infected with LLV or PLV, despite the lack of prechallenge neutralizing antibody activity against FIV. Thus, as compared with naive controls, cats previously infected with LLV or PLV were able to more effectively control FIV infection and resist its immunologic effects, despite the substantial genetic divergence between these lentiviruses-raising the possibility that superinfection may impart resistance to lentivirus infection by heightening innate immune mechanisms.

Animals↗
PubMed2002

Patterns of molecular genetic variation among African elephant populations.

The highly threatened African elephants have recently been subdivided into two species, Loxodonta africana (savannah or bush elephant) and L. cyclotis (forest elephant) based on morphological and molecular studies. A molecular genetic assessment of 16 microsatellite loci across 20 populations (189 individuals) affirms species level genetic differentiation and provides robust genotypic assessment of species affiliation. Savannah elephant populations show modest levels of phylogeographic subdivision based on composite microsatellite genotype, an indication of recent population isolation and restricted gene flow between locales. The savannah elephants show significantly lower genetic diversity than forest elephants, probably reflecting a founder effect in the recent history of the savannah species.

Africa South of the Sahara↗
PubMed2002

The trans-rotator cuff approach to SLAP lesions: technical aspects for repair and a clinical follow-up of 31 patients at a minimum of 2 years.

PURPOSE: To discuss a new technique for the surgical treatment of type II SLAP lesions as well as the evaluation of the technique's effectiveness with a minimum 2-year follow-up. TYPE OF STUDY: Retrospective clinical follow-up study. METHODS: We present a clinical follow-up of 31 patients who were treated arthroscopically for type II SLAP lesions using a trans-rotator cuff portal at an average follow-up time of 3.7 years. Patients were screened for concomitant procedures including rotator cuff repairs, shoulder stabilizations, thermal capsullographies, and previous surgeries. These patients were subsequently excluded from the study. Patients were given a standard physical examination of the upper extremity at our institution and they completed both the L'Isalata and American Shoulder and Elbow Surgeons questionnaires. RESULTS: All 31 patients identified were available for follow-up at an average time of 3.7 years postoperatively (range, 2.0 to 7.4 years). The average L'Insalata score was 87.0 points (range, 46.1-100 points); the average ASES score was 87.2 points (range, 46.7-100 points). The average pain score was 1.5 (range, 0-5) and only 4 of the 31 patients complained of moderate pain with activity. Sixteen of the 31 patients returned to their preinjury level of sports; 11 of the 31 patients returned to limited activity and 2 patients were inactive at the time of follow-up. Overall satisfaction with the procedure averaged 3.79 points (range, 0-5 points): 22 patients rated overall satisfaction as good or excellent, 6 patients reported a fair outcome, and only 3 patients were unsatisfied with the results of the surgery. One patient who was unsatisfied with the procedure had reinjured his superior labrum and required a second operation. None of the 31 patients had symptoms suggestive of rotator cuff pathology. Of the 30 patients found to have a positive Active Compression test preoperatively, 26 of these patients now had a negative sign. CONCLUSIONS: The trans-rotator cuff approach allows for a more optimal placement of a biodegradable fixation device and/or suture anchors into the superior labrum. Furthermore, we believe that this approach does not compromise the function of the rotator cuff. The trans-rotator cuff technique is an effective and safe modality to address superior labral pathology.

Accidents, Traffic↗
PubMed2002

The joint jack: report of a new technique essential for elbow arthroscopy.

Visualization and access are of fundamental importance in arthroscopy, including arthroscopy of the elbow. A new technique not previously described in the literature improves both of these factors for key areas within the elbow that would otherwise be inaccessible. This technique employs the application of gentle leverage to pry apart the surfaces of the ulnohumeral articulation when viewing and working posteriorly to improve visualization and access to the ulnohumeral and radiocapitellar articular spaces. We believe this technique is essential for full arthroscopic viewing of the intra-articular regions of the ulnohumeral and radiocapitellar joints.

Adult↗
PubMed2002

Arthroscopic removal of an osteoid osteoma of the shoulder.

Two cases of arthroscopic retrieval of intra-articular shoulder pathology are presented. With this technique, areas that are often difficult to expose in an open fashion and those previously deemed inaccessible arthroscopically are localized readily. In the setting of intra-articular pathology, thought should be given to the possibility of arthroscopic retrieval or excision before proceeding with open surgery.

Adult↗
PubMed2002

Negative prognostic factors in managing massive rotator cuff tears.

OBJECTIVE: To investigate the negative prognostic factors in the management of massive rotator cuff tears. DESIGN: Retrospective nonrandomized study. SETTING: Faculty Practice associated with a major orthopedic teaching hospital. PATIENTS: 108 patients who were treated for massive rotator cuff tears were evaluated for an average of 3.2 years posttreatment. There were 58 females and 50 males, with a mean age of 61.3 years. INTERVENTIONS: 40 patients underwent conservative nonsurgical management (Group 1), 32 patients underwent arthroscopic debridement (Group 2), and 36 patients underwent primary repair of the rotator cuff (Group 3). MAIN OUTCOME MEASURES: A detailed Shoulder Rating Questionnaire was filled out by patients pretreatment and minimal 2 years posttreatment. RESULTS: Overall, Group 1 had 65% excellent or good outcomes, Group 2 had 81%, and Group 3 had 86%. The subgroup of patients in Group 1 who had cortisone injections had a 75% success rate. CONCLUSIONS: Negative prognostic factors evaluated are presence of glenohumeral arthritis, decreased passive range of motion, superior migration of the humeral head, presence of atrophy, and external rotation/abduction strength less than 3. The presence of 3 or more of these negative prognostic factors are correlated with poor outcomes in the treatment of massive rotator cuff tears.

Activities of Daily Living↗
PubMed2002

Genomic microsatellites as evolutionary chronometers: a test in wild cats.

Nuclear microsatellite loci (2- to 5-bp tandem repeats) would seem to be ideal markers for population genetic monitoring because of their abundant polymorphism, wide dispersal in vertebrate genomes, near selective neutrality, and ease of assessment; however, questions about their mode of generation, mutation rates and ascertainment bias have limited interpretation considerably. We have assessed the patterns of genomic diversity for ninety feline microsatellite loci among previously characterized populations of cheetahs, lions and pumas in recapitulating demographic history. The results imply that the microsatellite diversity measures (heterozygosity, allele reconstitution and microsatellite allele variance) offer proportionate indicators, albeit with large variance, of historic population bottlenecks and founder effects. The observed rate of reconstruction of new alleles plus the growth in the breadth of microsatellite allele size (variance) was used here to develop genomic estimates of time intervals following historic founder events in cheetahs (12,000 yr ago), in North American pumas (10,000-17,000 yr ago), and in Asiatic lions of the Gir Forest (1000-4000 yr ago).

Acinonyx↗
PubMed2002

HLA-Cw*04 and hepatitis C virus persistence.

In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.

Adult↗