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Biomedical subjects

S J O'Brien

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

At least 307 records · Page 17Linked to original sources

One-stage bilateral total hip arthroplasty. A prospective study of perioperative morbidity.

Controversy exists over the safety of performing one-stage bilateral total hip arthroplasty. A prospective protocol was established in 35 patients to evaluate the perioperative morbidity of one-stage bilateral arthroplasty as compared with unilateral controls. Although there was no increase in the frequency of respiratory morbidity in bilateral procedures, respiratory depression is common with both procedures. The authors believe this is consistent with varying degrees of the adult respiratory distress syndrome and that the term fat embolism syndrome is misleading and should be abandoned.

Adult↗

Identification of an amplified, highly expressed gene in a human glioma.

A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a member of a select group of cellular genes that are genetically altered in primary human tumors.

Cell Line↗

Partial structure of the human alpha 2(IV) collagen chain and chromosomal localization of the gene (COL4A2).

We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the alpha 2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triple-helical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the alpha 1 and alpha 2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the alpha 1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the alpha 2(IV) cDNA probe with the gene for the alpha 1(IV) collagen chain. An EcoRI fragment characteristic of the alpha 2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the alpha 1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.

Amino Acid Sequence↗

Molecular analysis of integrated human papillomavirus 16 sequences in the cervical cancer cell line SiHa.

Human papillomavirus (HPV) 16 is frequently found integrated into cervical cancer cell genomes and these integrations are thought to play a role in tumorigenesis. To investigate the mechanisms of HPV integration and its effect on transcription and chromosomal sequence organization, we have cloned and analyzed the HPV16 integration from the cervical cancer cell line SiHa. Restriction analyses and Southern blotting indicated that approximately 95% of an HPV16 genome was integrated without gross rearrangement. Sequence analysis of the cellular-viral DNA junctions revealed that integration had occurred within the E2 and E4 ORFs where 251 bp of viral sequence was deleted. One viral terminus occurred within sequences of an Alu repeat and a 4-bp homology was present at the site of recombination. Using unique cellular flanking DNA probes, a 4.8-kb deletion of cellular sequences was detected at the site of viral integration. The chromosomal location of the viral integration and cellular deletion were mapped to chromosome 13 using a rodent X human somatic cell hybrid panel. Northern blot analysis using viral subgenomic and 3' cellular probes revealed transcription from the 3' portion of integrated HPV16 (E6, E7, E1) and flanking cellular sequences. The observation of viral-cell transcripts and chromosomal deletions associated with HPV integration may indicate that such events are part of a multistep mechanism leading to the development of cervical cancer.

Base Sequence↗

A molecular phylogeny of the hominoid primates as indicated by two-dimensional protein electrophoresis.

A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE). An internally consistent matrix of Nei genetic distances was generated on the basis of variants in electrophoretic position. The derived phylogenetic tree indicated a branching sequence, from oldest to most recent, of cercopithecoids (Macaca fascicularis), gibbon-siamang, orangutan, gorilla, and human-chimpanzee. A cladistic analysis of 240 electrophoretic characters that varied between ape species produced an identical tree. Genetic distance measures obtained by 2DE are largely consistent with those generated by other molecular procedures. In addition, the 2DE data set appears to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans.

Animals↗

The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.

The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

Chromosome Banding↗

East African cheetahs: evidence for two population bottlenecks?

A combined population genetic and reproductive analysis was undertaken to compare free-ranging cheetahs from east Africa (Acinonyx jubatus raineyi) with the genetically impoverished and reproductively impaired south African subspecies (Acinonyx jubatus jubatus). Like that of their south African counterparts, the quality of semen specimens from east African cheetahs was poor, with a low concentration of spermatozoa (25.3 X 10(6) per ejaculate) and a high incidence of morphological abnormalities (79%). From an electrophoretic survey of the products of 49 genetic loci in A. jubatus raineyi, two allozyme polymorphisms were detected; one of these, for a nonspecific esterase, shows an allele that is rare (less than 1% incidence) in south African specimens. Estimates of polymorphism (2-4%) and average heterozygosity (0.0004-0.014) affirm the cheetah as the least genetically variable felid species. The genetic distance between south and east African cheetahs was low (0.004), suggesting that the development of genetic uniformity preceded the recent geographic isolation of the subspecies. We propose that at least two population bottlenecks followed by inbreeding produced the modern cheetah species. The first and most extreme was ancient, possibly late Pleistocene (circa 10,000 years ago); the second was more recent (within the last century) and led to the south African populations.

Africa, Eastern↗

Similarity in ejaculate-endocrine characteristics in captive versus free-ranging cheetahs of two subspecies.

Ejaculate-endocrine characteristics were measured in 23 captive cheetahs (Acinonyx jubatus jubatus) in North American zoos and in 8 free-ranging cheetahs (A.j. raineyi) in eastern Africa (Tanzania). A standardized electroejaculation protocol was used, and numbers of motile spermatozoa were similar (p greater than 0.05) between groups. Of the spermatozoa collected by electroejaculation, 70.6 +/- 3.3% and 75.9 +/- 4.4% were morphologically abnormal in the captive "North American" and in the free-ranging, eastern African populations, respectively. Adrenal activity, as measured by an acute, temporal rise and fall in serum cortisol levels during and after electroejaculation, was no different (p greater than 0.05) between groups. Although serum luteinizing hormone (LH) levels were less (p less than 0.05) in the free-ranging than in the captive animals, serum testosterone concentrations were similar. The data indicate that the comparatively poor reproductive performance of cheetahs maintained in zoological parks is not attributable to a captivity-induced response afflicting the male. Furthermore, there is no evidence that ejaculate/endocrine characteristics differ between the two subspecies. Because adrenal/gonadal activity and the number of pleiomorphic spermatozoa are similar between the test groups, the results suggest that spermatozoal diversity originates as a result of the extreme genetic monomorphism observed universally in the species.

Acinonyx↗

Chromosomal evolution of the Canidae. I. Species with high diploid numbers.

The Giemsa banding patterns of seven canid species, including the grey wolf (Canis lupus), the maned wolf (Chrysocyon brachyurus), the bush dog (Speothos venaticus), the crab-eating fox (Cerdocyon thous), the grey fox (Urocyon cinereoargenteus), the bat-eared fox (Otocyon megalotis), and the fennec (Fennecus zerda), are presented and compared. Relative to other members of Canidae, these species have high diploid complements (2n greater than 64) consisting of largely acrocentric chromosomes. They show a considerable degree of chromosome homoeology, but relative to the grey wolf, each species is either missing chromosomes or has unique chromosomal additions and rearrangements. Differences in chromosome morphology among the seven species were used to reconstruct their phylogenetic history. The results suggest that the South American canids are closely related to each other and are derived from a wolf-like progenitor. The fennec and the bat-eared fox seem to be recent derivatives of a lineage that branched early from the wolf-like canids and which also includes the grey fox.

Animals↗

Chromosomal evolution of the Canidae. II. Divergence from the primitive carnivore karyotype.

The Giemsa-banding patterns of chromosomes from the arctic fox (Alopex lagopus), the red fox (Vulpes vulpes), the kit fox (Vulpes macrotis), and the raccoon dog (Nyctereutes procyonoides) are compared. Despite their traditional placement in different genera, the arctic fox and the kit fox have an identical chromosome morphology and G-banding pattern. The red fox has extensive chromosome arm homoeology with these two species, but has only two entire chromosomes in common. All three species share some chromosomes with the raccoon dog, as does the high diploid-numbered grey wolf (Canis lupus, 2n = 78). Moreover, some chromosomes of the raccoon dog show partial or complete homoeology with metacentric feline chromosomes which suggests that these are primitive canid chromosomes. We present the history of chromosomal rearrangements within the Canidae family based on the assumption that a metacentric-dominated karyotype is primitive for the group.

Animals↗

A comparative chromosome banding analysis of the Ursidae and their relationship to other carnivores.

Trypsin G-banded karyotypes of eight species of Ursidae were prepared from retrovirus-transformed skin fibroblast cultures. The banding patterns of all bears are highly conserved, even though their diploid numbers range from 42 to 72. A comprehensive analysis of the homologous banding patterns within the Ursidae and with a hypothesized ancestral carnivore karyotype permitted the reconstruction of three significant chromosomal reorganization events that occurred during the evolution of the modern ursids. The first was a multichromosomal fissioning away from the biarmed (2n = 44) primitive carnivore karyotype, leading to six species of the Ursinae subfamily (2n = 78). The second was a comprehensive chromosome fusion in the lineage that led to the Ailuropodinae (giant panda) subfamily (2n = 44). The third event was a second, independent, but less extensive, centromeric fusion occurring in the line that led to the Tremarctinae (spectacled bear) subfamily (2n = 52). Ursidae karyotypes are not only highly conserved within the family but also exhibit extensive chromosome banding homology with other carnivore families.

Animals↗

Anterior shoulder instability.

Current concepts for the diagnosis and treatment of anterior dislocation and subluxation, including classification of injuries, are presented. The pathophysiology, clinical and radiologic examination, and treatment protocols are discussed.

Arthroscopy↗

Posterior shoulder instability.

The incidence, basic pathophysiology, and clinical and radiologic examination in posterior instability of the shoulder are discussed. Conservative treatment protocols and surgical procedures are presented.

Humans↗