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Biomedical subjects

B Nixon

Publications and source records attributed to B Nixon.

12 recordsLinked to original sources
PubMed2006

First recorded pregnancy and normal birth after ICSI using electrophoretically isolated spermatozoa.

BACKGROUND: DNA damage in the male germ line is associated with poor fertilization and cleavage rates, impaired embryo quality and early pregnancy loss. Given these associations, embryologists are keen to develop techniques that will allow the selection of viable spermatozoa exhibiting low levels of DNA damage for assisted conception purposes. METHODS: In this article, we describe a novel electrophoretic approach for the rapid isolation of cells possessing little DNA damage. The limits of the method were examined using cryostored and snap-frozen semen samples as well as testicular biopsy material. In addition, clinical utility was demonstrated in a case study involving treatment of a patient exhibiting persistently high levels of DNA damage in his spermatozoa. RESULTS: From a range of difficult starting materials (biopsies, cryostored semen and snap-frozen sperm suspensions), the electrophoretic system rapidly isolated populations of motile, viable, morphologically normal spermatozoa exhibiting high levels of DNA integrity. Clinical application in a couple suffering from long-term infertility associated with extensive DNA damage in the male germ line led to the first human pregnancy following such electrophoretic sperm isolation. CONCLUSIONS: The electrophoretic procedure holds promise as a convenient method for the rapid preparation of high-quality spermatozoa for assisted conception purposes.

Cell Separation↗
PubMed2005

Development of a novel electrophoretic system for the isolation of human spermatozoa.

BACKGROUND: Optimization of assisted conception outcomes involves the development of rapid, safe, effective techniques for the isolation of functional human spermatozoa free from significant DNA damage. In this study we describe a novel electrophoretic sperm isolation technique that achieves these objectives. METHODS: The separation system consisted of a cassette comprising two 400 mul chambers separated by a polycarbonate filter containing 5 micromol/l pores and bounded by a 15 kDa polyacrylamide membrane to allow the free circulation of buffer. Semen was introduced into one chamber, current applied (75 mA at variable voltage) and within seconds a purified suspension of spermatozoa could be collected from the adjacent chamber. These cells were assessed for their count, viability, motility, morphology and DNA integrity. RESULTS: The suspensions generated by the electrophoretic separation technique contained motile, viable, morphologically normal spermatozoa and exhibited low levels of DNA damage. Moreover, these cell suspensions were free from contaminating cells, including leukocytes. The technique was comparable to discontinuous gradient centrifugation except that it took a fraction of the time and generated cells with significantly less DNA damage. CONCLUSION: Electrophoretic separation represents a highly effective, novel approach for the isolation of spermatozoa for assisted conception purposes.

Cell Separation↗
PubMed2001

Galactosyltransferase function during mammalian fertilization.

Gamete recognition has been studied extensively in the mouse. In this system, it is generally believed that sperm bind to a class of O-linked oligosaccharides on the zona pellucida glycoprotein, ZP3. The best characterized sperm receptor for ZP3 is beta1, 4-galactosyltransferase (GalT), which functions in a lectin-like capacity by binding to N-terminal N-acetylglucosamine residues on ZP3 oligosaccharides. Multivalent oligosaccharides on ZP3, as well as synthetic polymers terminating in N-acetylglucosamine aggregate GalT, leading to activation of a heterotrimeric G protein cascade and culminating in the acrosome reaction. Following fertilization, cortical granules release N-acetylglucosaminidase, which removes the binding site for sperm GalT and facilitates the zona block to polyspermic binding. Genetic manipulation of GalT expression has confirmed its function as a ZP3 receptor. Overexpressing GalT on sperm leads to increased binding of ZP3, increased G protein activation, and precocious acrosome reactions. In contrast, sperm from mice made null for GalT by homologous recombination are refractory to ZP3, in that they are unable to bind soluble ZP3 and fail to undergo the acrosome reaction in response to zona glycoproteins. Surprisingly, GalT null sperm still bind to the zona and achieve low rates of fertilization in vitro. This then suggests that sperm-egg binding involves receptor-ligand interactions independent of GalT and ZP3. The current model suggests that GalT functions as the ZP3 receptor that is responsible for inducing the acrosome reaction, whereas initial sperm-zona binding is dictated by other sperm surface receptors. Consistent with this, at least three other zona pellucida monosaccharides have been implicated in sperm binding, and novel sperm surface glycoproteins have been suggested to function in gamete binding. A large scaffolding protein has been identified that associates with the GalT cytoplasmic domain and may be responsible for orchestrating its signal transduction capacities that lead to the acrosome reaction.

Acrosome Reaction↗
PubMed1998

The specificity of epididymal secretory proteins.

Early studies in which the electrophoretic profiles of fluid from different regions of the epididymis were compared with other body fluids, such as blood serum, suggested that many proteins present in epididymal fluid were not found in other secretions and thus might be tissue specific. Comparative studies of epididymal fluid from different species further emphasized differences so that some epididymal proteins are considered both tissue and species specific. Such proteins are the putative molecular agents responsible for the array of changes undergone by spermatozoa during maturation. Thus a complete characterization of all the specific proteins secreted by the epididymis would yield important information for understanding the molecular events of maturation. Comparison of these proteins across species would determine whether the proteins and mechanisms at the centre of changes such as acquisition of fertilizing ability are conserved during evolution. This review critically examines the evidence for both tissue and species specificity of epididymal secreted proteins, describes how advances in molecular biology can be used to clarify this issue and concludes with a description of some preliminary work with different lagomorph species involving the REP 52 protein, an epididymal secretory protein that binds specifically to spermatozoa in New Zealand white rabbits.

Animals↗
PubMed1997

Examination of the immunocontraceptive potential of recombinant rabbit fertilin subunits in rabbit.

Recombinant fertilin subunits produced in a bacterial expression systems were used to test fertilin as an immunocontraceptive antigen in the European rabbit (Oryctolagus cuniculus). Wild female rabbits (n = 40) were immunized with either recombinant rabbit fertilin alpha or beta subunits by the s.c. or intra-Peyer's patch route. High titers of serum anti-fertilin polyclonal IgG antibodies were achieved in all rabbits after repeated boosts, with fertilin-specific IgG but not IgA antibodies detected in vaginal lavages of all animals. The serum IgG antibodies recognized polypeptides in detergent extracts of rabbit sperm with relative molecular masses of 48, 53, and 85 kDa on reducing SDS-PAGE gels and were shown to bind to the head region of methanol-fixed and live caudal rabbit sperm. Preincubation of rabbit sperm with these anti-fertilin IgG antibodies at concentrations of 400 micrograms/ml blocked sperm binding to zona-intact oocytes and inhibited fertilization in vitro by 60-80%. However, despite the levels of circulating and vaginal IgG antibodies achieved, only 4 immunized does failed to become pregnant out of 33 that ovulated. The remaining animals either showed no effect on fertility (n = 29) relative to control animals or failed to ovulate (n = 7). All control animals ovulated and were either fully fertile (n = 15) or were mated to infertile males (n = 4). In addition, proven-fertile male domestic rabbits (n = 3) were immunized s.c. and boosted three times with fertilin beta. Only one animal subsequently showed impaired fertility. These results show that in the rabbit, high levels of circulating sperm-reactive anti-fertilin antibodies and the presence of vaginal IgG does not ensure infertility.

ADAM Proteins↗
PubMedDate not supplied

Effect of local corticosteroids on early inflammatory function in surgical wound of rats.

To investigate the effects of local corticosteroids during the early inflammatory process in iatrogenically induced surgical wounds, three different types of corticosteroids, dexamethasone sodium phosphate (Decadron), betamethasone sodium phosphate (Celestone Phosphate), and betamethasone sodium phosphate-acetate (Celestone Soluspan), were evaluated using rats. Single doses of corticosteroid were administered locally to male Sprague-Dawley rats after the surgical implantation of a wound chamber, which was used to collect fluid from the surrounding surgical wound. Wound fluids were drawn from the wound chamber at postoperative days 1, 3, and 5 and analyzed for total white blood cells (WBCs) and differential count. In this study, the authors have demonstrated that the corticosteroids (dexamethasone sodium phosphate, betamethasone sodium phosphate, betamethasone sodium phosphate-acetate) cause at least 50% reduction in the total circulating WBCs at the surgical wound site on postoperative day 1, followed by decreased reductions on days 3 and 5.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Unusual case of postoperative infection caused by Morganella morganii.

Morganella morganii is a facultative Gram-negative anaerobe present in the human gastrointestinal system as normal flora. Clinically, the organism is important when it manifests as an opportunistic pathogenic infection elsewhere in the body. This paper reviews an unusual case in which M. morganii is the pathogen responsible for a devastating postoperative infection in a diabetic patient. Currently, there are no known reported cases in the literature of M. morganii as an etiologic pathogen for a postoperative foot infection. Prompt diagnosis and treatment of this organism is imperative to reduce the patient's overall morbidity and mortality.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Tumoral calcinosis of the foot: case report and literature review.

Soft tissue tumors occur in all parts of the body. Once identified, they must be thoroughly evaluated and treated. Tumoral calcinosis is a metabolic disorder that presents as a soft tissue deposit near large joints in the body. Occasionally, it may occur in the foot and become symptomatic. Once the etiology and pathophysiology is understood, the proper course of treatment may begin.

Adult↗