Biomedical subjects
Publications and source records attributed to S J O'Brien.
The gene for the fibroblast growth factor receptor BEK was assigned to human chromosome 10 by applying polymerase chain reaction techniques to DNAs from a panel of human x rodent somatic cell hybrids. The gene was further localized to 10q25.3----q26 by in situ hybridization.
We report a case of peroneal tendon subluxation as a result of an anomalous extension of the peroneus brevis muscle into the fibular groove, causing an encroachment phenomenon, stretching-out of the superior peroneal retinaculum, longitudinal splitting of the peroneus brevis tendon, subluxation of the peroneal tendons, and peroneal tenosynovitis. We describe a simple surgical technique for tendon stabilization, after decompression of the fibular groove.
Evolutionary homologs of the ets proto-oncogene have been discovered in the genomes of widely divergent eucaryote species from Drosophila to sea urchin to vertebrates. The prototype mammalian ets-1 and ets-2 genes are divided into three coding domains that differ in their rate of accumulation of sequence divergence. An analysis of sequence divergence of ets gene homologs in various species has produced a phylogenetic history of the ets gene family in the context of metazoan evolutionary radiation. A minimum of five duplication events of ets primordial genes were evident, namely (1) a duplication that separates primitive ets genes (Drosophila precursor of 74E, mouse PU.1 and human ELK1) from the ets-1, ets-2, erg ancestor; (2) and (3) two duplications that established separate ets, erg and elg/GABP-alpha lineages which occurred prior to invertebrate-vertebrate divergence; (4) divergence of ets-1 and ets-2 gene family also associated with vertebrate-invertebrate divergence; (5) duplication of ets-1 and ets-2 in Xenopus laevis to produce two ets-1 genes and two ets-2 genes during genomic tetraploidation in the recent ancestry of this species.
We studied the gross, histological, and vascular anatomy of the glenoid labrum in twenty-three fresh-frozen shoulders from cadavera to demonstrate its cross-sectional anatomy, its microvascularity, and its attachments. The superior and anterosuperior portions of the labrum are loosely attached to the glenoid, and the macro-anatomy of those portions is similar to that of the meniscus of the knee. The superior portion of the labrum also consistently inserts directly into the biceps tendon, while its inferior portion is firmly attached to the glenoid rim and appears as a fibrous, immobile extension of the articular cartilage. The arteries supplying the periphery of the glenoid labrum come from the suprascapular, circumflex scapular, and posterior circumflex humeral arteries. In general, the superior and anterosuperior parts of the labrum have less vascularity than do the posterosuperior and inferior parts, and the vascularity is limited to the periphery of the labrum. Vessels supplying the labrum originate from either capsular or periosteal vessels and not from the underlying bone.
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Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etudé du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.
The influence of culture medium and protein supplements on in vitro fertilization (IVF) and morula-to-blastocyst development in culture was examined in the domestic cat. In Study I, follicular oocytes were fertilized and cultured in 1) modified Krebs Ringer bicarbonate (mKRB); 2) modified Tyrode's solution (TALP) without phosphate or glucose; or 3) Ham's F10. All media contained bovine serum albumin (BSA). Fertilization rates were similar (P greater than .05) among mKRB (75.0%), TALP (70.6%), and Ham's F10 (80.0%) treatments. Compared to TALP (77.8%), more (P less than .05) embryos in Ham's F10 (95.0%) developed to the morula stage; development of mKRB embryos (88.9%) was intermediate and not different (P greater than .05). Study II evaluated the effects of protein availability and type on IVF and embryo growth. Ham's F10 was supplemented with polyvinylalcohol (PVA, 2 mg/ml), BSA (4 mg/ml), fetal calf serum (FCS, 5%), or estrous cat serum (ECS, 5%) and used to fertilize and culture embryos. Fertilization was enhanced (P less than .05) using either FCS (84.0%) or ECS (85.2%) compared to PVA (67.3%). Oocytes exposed to BSA fertilized at a rate (76.1%) similar (P greater than .05) to other treatments. Embryos exposed to all four treatment groups (PVA, 82.8%; BSA, 82.8%; FCS, 92.9%; or ECS, 97.8%) were equally capable (P greater than .05) of becoming morulae. However, more FCS- or ECS-supplemented morulae continued to the early blastocyst stage (30.8%, 22.2%, respectively, P less than .05) than PVA- (10.3%) or BSA- (13.8%) exposed morulae. In the domestic cat IVF system, the type of medium and protein supplement used appears to have a greater impact on embryo development in vitro than on fertilization.(ABSTRACT TRUNCATED AT 250 WORDS)
A small colony of feral mice from California continues to flourish in spite of a virulent epizootic of pathological retrovirus. Epidemiological and genetic studies revealed that the viral infection is strongly balanced by the polymorphic resistance locus, Fv-4, a transcriptionally active but truncated provirus that originated in the East Asian ancestors of the Californian mice. The natural history of these populations represents a graphic example of genomic adaptation in free-ranging populations to regulate and delimit infectious disease.
Nineteen polymorphic lymphocyte proteins were previously detected by two-dimensional protein electrophoresis (2DE). In this report, we describe the genetic linkage mapping of six of these polymorphic proteins (PNIA1-PNIA6), the identification by genetic linkage of a seventh (glyoxalase 1 on 6p21), and support for the mapping of an eighth (plastin or LCP1) to near the ESD locus on Chr 13. PNIA1-PNIA6 were assigned, respectively, to 10q26, 16p13.3, 10q, 11p15, 3q, and 19q13. These genetic linkages were achieved by classical linkage analysis of 2DE protein charge polymorphisms to the panel of RFLPs previously typed in nine pedigrees in the Centre D'Etude du Polymorphisme Humain (CEPH) collection.
The feline homolog to the mammalian homeobox locus, HOX3A, was isolated by screening a domestic cat genomic library with the murine Hox-3.1 probe. The nucleotide sequence similarity of the feline homeobox was 96% to human HOX3A, 94% to mouse Hox-3.1, and 94% to rat R4. The deduced amino acid sequence (homeodomain) of this feline homeobox was identical to all homeodomains of these cognate genes. Using a panel of feline x rodent somatic cell hybrids, the HOX3A locus was assigned to feline chromosome B4. Human HOX3A and mouse Hox-3.1 have been mapped previously to human chromosome 12 and mouse chromosome 15, respectively, both of which share syntenic homology to feline chromosome B4. These data demonstrate evolutionary conservation of both HOX3A gene sequences and chromosomal location during mammalian evolution.
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The recent emphasis on human genome mapping has stimulated the development of gene maps in close to thirty mammalian species. Animal gene maps provide an invaluable resource for genetic analysis and manipulation of phenotypic characters, as well as a retrospective glimpse at the patterns and processes of genome evolution. An empirical strategy for developing new gene maps in mammals by emphasizing two important classes of index or anchor marker loci is presented.
Some researchers have suggested that about 50% of aging decline is preventable through improved life-style habits such as participation in regular exercise, yet exercise as a resource for healthier survival is being ignored by many aging women. Though recent research findings highlight regular physical activity as a potent factor in combatting hypokinesis (the disease of inactivity), numerous real and perceived barriers to exercise stand between the older woman and her ability to achieve a better quality of life. Among strategies that have been developed to overcome these barriers are social empowerment initiatives that may encourage women to combat disability by engaging in regular exercise.
Numerous studies have used indices of genetic distance between species to reconstruct evolutionary relationships and to estimate divergence time. However, the empirical relationship between molecular-based indices of genetic divergence and divergence time based on the fossil record is poorly known. To date, the results of empirical studies conflict and are difficult to compare because they differ widely in their choice of taxa, genetic techniques, or methods for calibrating rates of molecular evolution. We use a single methodology to analyze the relationship of molecular distance and divergence time in 86 taxa (72 carnivores and 14 primates). These taxa have divergence times of 0.01-55 Myr and provide a graded series of phylogenetic divergences such that the shape of the curve relating genetic distance and divergence time is often well defined. The techniques used to obtain genetic distance estimates include one- and two-dimensional protein electrophoresis, DNA hybridization, and microcomplement fixation. Our results suggest that estimates of molecular distance and divergence time are highly correlated. However, rates of molecular evolution are not constant; rather, in general they decline with increasing divergence time in a linear fashion. The rate of decline may differ according to technique and taxa. Moreover, in some cases the variability in evolutionary rates changes with increasing divergence time such that the accuracy of nodes in a phylogenetic tree varies predictably with time.
The potential for rescuing immature oocytes from the ovaries of females of rare felid species which die or undergo medical ovariohysterectomy was evaluated. Ovaries were recovered from 13 species representing 35 individuals in good-to-poor health. Although the majority of females were 10 yr of age or older and in fair-to-poor health, a total of 846 oocytes were recovered of which 608 (71.9%) were classified as fair-to-excellent quality. One hundred of these oocytes were used for initial maturation classification and as parthogenetic controls. Overall, of the 508 fair-to-excellent quality oocytes placed in culture, 164 (32.3%) matured to metaphase II in vitro. For species in which 3 or more individuals yielded oocytes, mean oocyte maturation rates were as follows: 36.2%, tiger; 27.9% leopard; and 8.3%, cheetah. In vitro insemination of oocytes resulted in fertilization (2 polar bodies, 2 pronuclei, or cleavage) rates of 9.1% to 28.6% (leopard) using homologous fresh spermatozoa and 4.0% (lion) to 40.0% (puma) using homologous frozen-thawed spermatozoa. Inseminations using heterologous (domestic cat) spermatozoa also resulted in fertilized oocytes in the tiger, leopard, snow leopard, puma, serval, and Geoffroy's cat (range in fertilization rate, 5.0% for leopard to 46.2% for puma). Cleaved embryos resulted from the insemination of leopard oocytes with homologous sperm (n = 1 embryo) and puma oocytes with domestic cat sperm (n = 3 embryos). These results demonstrate that immature ovarian oocytes from rare felid species can be stimulated to mature in vitro despite an excision-to-culture interval as long as 36 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Pituitary-gonadal function was examined in male lions free-ranging in the Serengeti Plains or geographically isolated in the Ngorongoro Crater of Tanzania. Lions were classified by age as adult (6.1-9.8 years), young adult (3.3-4.5 years) or prepubertal (1.4-1.6 years, Serengeti Plains only). Each animal was anaesthetized and then bled at 5-min intervals for 100 min before and 140 min after i.v. administration of saline or GnRH (1 micrograms/kg body weight). Basal serum LH and FSH concentrations were similar (P greater than 0.05) among age classes and between locations. In Serengeti Plains lions, net LH peak concentrations after GnRH were approximately 35% greater (P less than 0.05) in prepubertal than in either adult or young adult animals. GnRH-stimulated LH release was similar (P greater than 0.05) between adult and young adult lions, and these responses were similar (P greater than 0.05) to those measured in Ngorongoro Crater lions. Basal and GnRH-stimulated testosterone secretion was higher (P less than 0.05) in adult than in young adult lions and lowest (P less than 0.05) in prepubertal lions. Age-class differences in testosterone production were related directly to the concentrations of LH receptors in the testis (P less than 0.05). Basal and GnRH-stimulated testosterone secretion and gonadotrophin receptor concentrations within age classes were similar (P greater than 0.05) between lions of the Serengeti Plains and Ngorongoro Crater. Lower motility and higher percentages of structurally abnormal spermatozoa were observed in electroejaculates of young adult compared to adult Serengeti Plains males (P less than 0.05) and were associated with decreased steroidogenic activity. In contrast, there were no age-related differences in ejaculate characteristics of Ngorongoro Crater lions. Seminal quality in the Crater population was poor in adult and young adult animals and was unrelated to alterations in pituitary or testicular function. In summary, only seminal quality in adult male lions was affected by location, whereas age significantly affected both basal and GnRH-stimulated testosterone secretion and seminal quality (Serengeti Plains only) in sexually mature males. The striking seminal/endocrine differences among pride (breeding) males of different ages raises questions about the impact of age on individual reproductive performance in this species.
Spermic electroejaculates (range in motile sperm/ejaculate, 0.50-122.9 x 10(6); mean +/- s.e.m., 38.6 +/- 4.9) were recovered from 47 of 48 adult koalas captured from 3 wild populations in Australia. Semen was characterized by (i) a high density of globular bodies, which prevented the estimation of sperm motility without dilution; (ii) a brownish colour; and (iii) an acidic pH. Spermatozoa were categorized on the basis of 10 head forms, most cells being a curved or hooked shape. The koala populations differed in sperm concentration and motility ratings, but not in testes size, testosterone production or proportions of spermatozoa with various head shapes. These data confirm that free-living koalas normally produce spermatozoa with a high incidence of structural heterogeneity almost solely confined to the head region; and demonstrate the utility and safety of conventional gamete and endocrine studies, approaches which will be useful for determining the impact of genetic isolation and venereal disease on species fertility.