Search PubMed⌕ Search

Biomedical subjects

S J O'Brien

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

At least 91 records · Page 5Linked to original sources

Rates of nuclear and cytoplasmic mitochondrial DNA sequence divergence in mammals.

Differential rates of nucleotide substitution among different gene segments and between distinct evolutionary lineages is well documented among mitochondrial genes and is likely a consequence of locus-specific selective constraints that delimit mutational divergence over evolutionary time. We compared sequence variation of 18 homologous loci (15 coding genes and 3 parts of the control region) among 10 mammalian mitochondrial DNA genomes which allowed us to describe different mitochondrial evolutionary patterns and to produce an estimation of the relative order of gene divergence. The relative rates of divergence of mitochondrial DNA genes in the family Felidae were estimated by comparing their divergence from homologous counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced "new might"), a genomic fossil that represents an ancient transfer of 7.9 kb of mitochondrial DNA to the nuclear genome of an ancestral species of the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial (mtDNA) sequences with multiple outgroup species were conducted to date the ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes and to calibrate the rate of sequence divergence of mitochondrial genes relative to nuclear homologous counterparts. By setting the fastest substitution rate as strictly mutational, an empirical "selective retardation index" is computed to quantify the sum of all constraints, selective and otherwise, that limit sequence divergence of mitochondrial gene sequences over time.

Animals↗

Evolutionary analysis of the 5'-terminal region of hepatitis G virus isolated from different regions in China.

We have determined the nucleotide sequence of the 5'-terminal region of the hepatitis G virus (HGV) genome in 11 hepatitis patients from three cities in China. Phylogenetic analyses revealed that the Chinese isolates were genetically distinct from previously described West African isolates (type 1) and American, European and East African isolates (type 2), with a mean sequence divergence of approximately 10%. The mean divergence between isolates from Lanzhou, in the northwest of China, and those from Shanghai and Nanjing, on the east coast of China, was 5% (range 3-7%). The isolates from Shanghai and Nanjing were closely related to a common strain in Japan, while some of those from Lanzhou were closely related to a southeast Asian type 3 isolate. Thus, the Chinese isolates belong to the type 3 variant of HGV.

Base Sequence↗

Infectivity of lion and puma lentiviruses for domestic cats.

Infection of domestic cats with feline immunodeficiency virus (FIV) causes progressive immunological deterioration similar to that caused by human immunodeficiency virus (HIV). Lentiviruses related to but phylogenetically distinct from FIV have been detected in several non-domestic feline species. Serological cross-reactivity of these viruses raises the question as to whether inter-species transmission may occur. To address this issue, we asked whether lion lentivirus (FIV-Ple) or two strains of puma lentivirus (FIV-Pco) could replicate or cause disease in domestic cats. We found that domestic cats inoculated with FIV-Ple developed persistent cell-associated viraemia, transient cell-free viraemia and antiviral antibody. Clinical disease was not detected throughout a 6 month observation period. Two of four cats inoculated with FIV-Pco developed cell-associated viraemia, seroconverted and exhibited transient lymphadenopathy. No changes in white blood cell parameters or other haematological abnormalities were detected in any of the infected cats. Virus-specific RNA was detected in co-cultivated lymphocytes of all infected cats by RT-PCR. These findings reveal that non-domestic cat lentiviruses are infectious for domestic cats and can establish persistent infection in the absence of disease.

Animals↗

Conservation of human vs. feline genome organization revealed by reciprocal chromosome painting.

We employed fluorescence in situ hybridization (FISH) with probes established by flow sorting metaphase chromosomes of the domestic cat (Felis cattus, 2n = 38) to "paint" homologous segments on human chromosomes and, reciprocally, using human chromosome paints on feline metaphase preparations. The results revealed, by direct microscopic observation, widespread conservation of genome organization between the two mammalian orders and confirmed 90% of the homologous genes mapped to both species. Fourteen of 23 human chomosomes were hybridized with single cat probes, and 9 of 19 cat chromosomes were entirely labeled by a single human probe. All other chromosomes were labeled with only two or, at most, three probes of the respective species. Y-chromosome probes gave no signals. Approximately 30 syntenic segments were identified, and the number of translocations could be estimated to be on the order of one new translocation per 10 million years in the phylogenetic lines leading to human and cat. Using the principle of maximum parsimony, the primitive vs. derived human chromosome segments were identified by comparison to the feline, cattle, and pig genomes, a first step in reconstructing the evolutionary heritage of the mammalian radiations. The results suggest that reciprocal chromosome painting will help reconstruct the history of genomic changes by determining the polarity of chromosomal rearrangements and establishing the ancestral karyotype for each principle branching point in mammalian evolution.

Animals↗

Suprascapular neuropathy. Results of non-operative treatment.

We retrospectively reviewed the results of non-operative treatment of suprascapular neuropathy in fifteen patients seen between November 1983 and February 1991. The clinical diagnosis was confirmed with electrodiagnostic studies. The treatment consisted of a program of physical therapy to improve the range of motion of the shoulder and to strengthen the surrounding muscles. The average duration of follow-up was three years and eleven months (range, one year to eight years and ten months). The latest evaluation included electrodiagnostic studies of the affected extremity and dynamic isokinetic testing of both upper extremities. The result was excellent for five patients and good for seven. The three remaining patients had operative treatment because of persistent symptoms; one of these patients had an excellent result, one had a good result, and one had a poor result. The results suggest that, in the absence of a well defined lesion producing mechanical compression of the suprascapular nerve, suprascapular neuropathy should be treated non-operatively.

Adolescent↗

Biomechanical evaluation of the medial collateral ligament of the elbow.

UNLABELLED: Anatomical dissection and biomechanical testing were used to study twenty-eight cadaveric elbows in order to determine the role of the medial collateral ligament under valgus loading. The medial collateral ligament was composed of anterior, posterior, and occasionally transverse bundles. The anterior bundle was, in turn, composed of anterior and posterior bands that tightened in reciprocal fashion as the elbow was flexed and extended. Sequential cutting of the ligament was performed while rotation caused by valgus torque was measured. The anterior band of the anterior bundle was the primary restraint to valgus rotation at 30, 60, and 90 degrees of flexion and was a co-primary restraint at 120 degrees of flexion. The posterior band of the anterior bundle was a co-primary restraint at 120 degrees of flexion and a secondary restraint at 30 and 90 degrees of flexion. The posterior bundle was a secondary restraint at 30 degrees only. The reciprocal anterior and posterior bands have distinct biomechanical roles and theoretically may be injured separately. The anterior band was more vulnerable to valgus overload when the elbow was extended, whereas the posterior band was more vulnerable when the elbow was flexed. The posterior bundle was not vulnerable to valgus overload unless the anterior bundle was completely disrupted. The intact elbows rotated a mean of 3.6 degrees between the neutral position and the two-newton-meter valgus torque position. Cutting of the entire anterior bundle caused an additional 3.2 degrees of rotation at 90 degrees of flexion, where the effect was greatest. CLINICAL RELEVANCE: Physical findings in a patient who has an injury of the anterior bundle may be subtle, and an examination should be performed with the elbow in 90 degrees of flexion for greatest sensitivity. As the anterior bundle is the major restraint to valgus rotation, reconstructive procedures should focus on anatomical reproduction of that structure. Parallel limbs of tendon graft placed from the inferior aspect of the medial epicondyle to the area of the sublimis tubercle will simulate the reciprocal bands of the anterior bundle. Temporary immobilization with the elbow in flexion may relax the critically important anterior band of the reconstruction during healing.

Biomechanical Phenomena↗

Genetic individualization of domestic cats using feline STR loci for forensic applications.

A group of ten short tandem repeat (STR) loci suitable for PCR typing from DNA of domestic cats is evaluated for genetic individualization using blinded samples of eight putative feline blood specimens. The ten loci were also typed in a 70 member cat pedigree to demonstrate Mendelian inheritance and independent assortment. A "match window" or measurement precision estimate was empirically established by determining the maximum gel migration difference among alleles identical by descent in different individuals of the pedigree. Hardy-Weinberg equilibrium and abundant heterozygosity was observed for each locus in cat population samples from Canada and the USA. The probabilities of two unrelated individuals matching by chance (Pm) at all ten loci was estimated as 1.35 x 10(-10). We present a conservative approach to compute, for forensic consideration, the mathematical likelihood of a chance genotypic match between DNA evidence from a crime scene and the suspect composite STR genotypes for species or populations when genotype frequency information is not available.

Animals↗

Genomic differentiation among natural populations of orang-utan (Pongo pygmaeus).

BACKGROUND: Orang-utans exist today in small isolated populations on the islands of Borneo (subspecies Pongo pygmaeus pygmaeus) and Sumatra (subspecies P. p. abelii). Although, on the basis of their morphological, behavioral and cytogenetical characteristics, the Bornean and Sumatran orang-utan populations are generally considered as two separate subspecies, there is no universal agreement as to whether their genetic differentiation is sufficient to consider and manage them as species, subspecies or population level taxonomic units. A more precise phylogenetic description would affect many conservation management decisions about captive and free-ranging orang-utans. RESULTS: We analyzed the amount and patterns of molecular genetic variation in orang-utan populations using cellular DNA from orang-utans from two locations in Sumatra and nine locations-representing four isolated populations-in Borneo. Genetic and phylogenetic analyses of mitochondrial DNA restriction fragment length polymorphisms, nuclear minisatellite (or variable number tandem repeat) loci and mitochondrial 16S ribosomal RNA sequences led to three major findings. First, the genetic distance and phylogenetic differentiation between Sumatran and Bornean orang-utans is large, greater than that between the common chimpanzee, Pan troglodytes, and the pygmy chimpanzee or bonobo, Pan paniscus. The genetic distance suggests that the two island subspecies diverged approximately 1.5-1.7 million years ago, well before the two islands separated and long enough for species-level differentiation. Second, there is considerable endemic genetic diversity within the Bornean and Sumatran orang-utan populations, suggesting that they have not experienced recent bottlenecks or founder effects. And third, there is little genetic differentiation among four geographically isolated populations of Bornean orang-utans, consistent with gene flow having occurred between them until recently. CONCLUSIONS: Our results are consistent with the view that the genetic differentiation between Sumatran and Bornean orang-utans has reached the level of distinct species. Furthermore, our findings indicate that there is not a genetic imperative for the separate management of geographically isolated Bornean populations.

Animals↗

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Acquired Immunodeficiency Syndrome↗

Complete nucleotide sequences of the domestic cat (Felis catus) mitochondrial genome and a transposed mtDNA tandem repeat (Numt) in the nuclear genome.

The complete 17,009-bp mitochondrial genome of the domestic cat, Felis catus, has been sequenced and conforms largely to the typical organization of previously characterized mammalian mtDNAs. Codon usage and base composition also followed canonical vertebrate patterns, except for an unusual ATC (non-AUG) codon initiating the NADH dehydrogenase subunit 2 (ND2) gene. Two distinct repetitive motifs at opposite ends of the control region contribute to the relatively large size (1559 bp) of this carnivore mtDNA. Alignment of the feline mtDNA genome to a homologous 7946-bp nuclear mtDNA tandem repeat DNA sequence in the cat, Numt, indicates simple repeat motifs associated with insertion/deletion mutations. Overall DNA sequence divergence between Numt and cytoplasmic mtDNA sequence was only 5.1%. Substitutions predominate at the third codon position of homologous feline protein genes. Phylogenetic analysis of mitochondrial gene sequences confirms the recent transfer of the cytoplasmic mtDNA sequences to the domestic cat nucleus and recapitulates evolutionary relationships between mammal species.

Amino Acid Sequence↗

A canine distemper virus epidemic in Serengeti lions (Panthera leo).

Canine distemper virus (CDV) is thought to have caused several fatal epidemics in canids within the Serengeti-Mara ecosystem of East Africa, affecting silver-backed jackals (Canis mesomelas) and bat-eared foxes (Otocyon megalotis) in 1978 (ref. 1), and African wild dogs (Lycaon pictus) in 1991 (refs 2, 3). The large, closely monitored Serengeti lion population was not affected in these epidemics. However, an epidemic caused by a morbillivirus closely related to CDV emerged abruptly in the lion population of the Serengeti National Park, Tanzania, in early 1994, resulting in fatal neurological disease characterized by grand mal seizures and myoclonus; the lions that died had encephalitis and pneumonia. Here we report the identification of CDV from these lions, and the close phylogenetic relationship between CDV isolates from lions and domestic dogs. By August 1994, 85% of the Serengeti lion population had anti-CDV antibodies, and the epidemic spread north to lions in the Maasai Mara National reserve, Kenya, and uncounted hyaenas, bat-eared foxes, and leopards were also affected.

Amino Acid Sequence↗

Molecular phylogeny of mitochondrial cytochrome b and 12S rRNA sequences in the Felidae: ocelot and domestic cat lineages.

Molecular phylogeny of the cat family Felidae is derived using two mitochondrial genes, cytochrome b and 12S rRNA. Phylogenetic methods of weighted maximum parsimony and minimum evolution estimated by neighbor-joining are employed to reconstruct topologies among 20 extant felid species. Sequence analyses of 363 bp of cytochrome b and 376 bp of the 12S rRNA genes yielded average pair-wise similarity values between felids ranging from 94 to 99% and from 85 to 99%, respectively. Phylogenetic reconstruction supports more recent, intralineage associations but fails to completely resolve interlineage relationships. Both genes produce a monophyletic group of Felis species but vary in the placement of the pallas cat. The ocelot lineage represents an early divergence within the Felidae, with strong associations between ocelot and margay, Geoffroy's cat and kodkod, and pampas cat and tigrina. Implications of the relative recency of felid evolution, presence of ancestral polymorphisms, and influence of outgroups in placement of the topological root are discussed.

Amino Acid Sequence↗

How long is too long? Determining the early management of meningococcal disease in Birmingham.

OBJECTIVE: To determine the length of time cases of meningococcal disease wait before receiving parenteral antibiotic therapy in hospital. METHOD: The hospital case notes of residents of Birmingham who were admitted to local hospitals in 1993 and discharged with a diagnosis of meningitis or meningococcal disease were reviewed. This information was combined with that held by the West Midlands Ambulance Service. RESULTS: Forty out of the 82 patients (49%) who met the case definition had meningococcal infection. Twenty one patients (26%) were admitted by ambulance, 11 of whom had meningococcal infection. The mean time from a request for an ambulance to the patient reaching hospital was 52 min for those with meningococcal infection compared to 55 min for those without. Nineteen patients (47.5%) with meningococcal infection waited more than one hour after admission for antibiotic treatment. Seven had an initial diagnosis of meningitis or meningococcal infection. Ten out of 27 patients with a meningococcal rash (37%), 13 out of 22 patients aged under five years (59%) and 13 out of 24 patients with microbiologically confirmed meningococcal infection (54%) waited more than one hour for treatment. Seven patients with meningococcal infection received benzyl penicillin before admission. Six received hospital antibiotic treatment within the hour. CONCLUSION: The assumption that patients suspected of having meningitis or meningococcal disease are treated promptly once in hospital is not always correct. The results of this study reinforce the need for all doctors to give benzyl penicillin promptly to patients they suspect have meningococcal disease.

Anti-Bacterial Agents↗