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Biomedical subjects

D Falconer

Publications and source records attributed to D Falconer.

9 recordsLinked to original sources
PubMed2004

Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover.

BACKGROUND: IVF is limited by low success rates and an unacceptably high multiple pregnancy rate. These outcomes would be improved significantly if a single embryo of high viability could be replaced in each treatment cycle, but widespread acceptance of such a policy is hindered by the lack of predictive factors for embryo selection. We have conducted a retrospective clinical study of a novel non-invasive method of embryo selection based on the depletion/appearance of amino acids in the culture medium. METHODS: Fifty-three cycles of IVF treatment using ICSI were studied. Embryos were cultured for 24 h in 4 microl drops of medium containing a physiological mixture of 18 amino acids. The spent medium was analysed for amino acid content by high performance liquid chromatography. RESULTS: The turnover of three amino acids, Asn, Gly and Leu, was significantly correlated with a clinical pregnancy and live birth. These correlations were independent of known predictors, such as female age, basal levels of FSH, embryo cell number and embryo morphological grade. CONCLUSIONS: Non-invasive assay of amino acid turnover has the potential to improve significantly the prospective selection of the most viable embryos, or single embryo, for replacement in an IVF cycle.

Adult↗
PubMed1999

Cloning, sequencing, expression and allelic sequence diversity of ERG3 (C-5 sterol desaturase gene) in Candida albicans.

The C-5 sterol desaturase gene (ERG3), essential for yeast ergosterol biosynthesis, was cloned and sequenced from Candida albicans by homology with the Saccharomyces cerevisiae ERG3. The ERG3 ORF contained 1158bp and encoded 386 deduced amino acids. The clone was used to transform a gal1 mutant derived from the Darlington strain of C. albicans, using galactose selection. The Darlington strain is known to lack Delta(5,6) sterols, i.e. to have an erg3 phenotype (Howell, S.A., et al., 1990. J. Appl. Bacteriol. 69, 692-696). The transformant (CDTR1) contained six tandem integrated ERG3GAL1 repeats, had double the abundance of ERG3 transcript found in the host strain, and synthesized ergosterol, a Delta(5,6) sterol.The Darlington strain was noted to have an abundance of ERG3 transcript. Both ERG3 alleles in Darlington were cloned and sequenced in order to look for changes that might explain the erg3 phenotype. One allele, called Dar-2, contained a stop codon in place of tryptophan-292. The other ERG3 allele, called Dar-1, had changes in three amino acids, two of which were conserved in three fungal and one plant species. EcoRI genomic fragments containing ERG3 from the Dar-1 allele and from B311, the wild-type strain, were inserted into the plasmid pRS316 and used to transform a Saccharomyces cerevisiae erg3,ura3 mutant using uracil selection. The 4.1kb ERG3 fragments from the B311 and Dar-1 both contained 1. 4kb 5' and 1.5kb 3' flanking sequences around the coding region. Transformants with ERG3 from B311 but not from Dar-1 showed restored ergosterol synthesis. One or more of these three deduced amino acids in the Dar-1 allele of ERG3 appeared critical for function.

Amino Acid Sequence↗
PubMed1998

Mechanism of fluconazole resistance in Candida krusei.

The mechanisms of fluconazole resistance in three clinical isolates of Candida krusei were investigated. Analysis of sterols of organisms grown in the absence and presence of fluconazole demonstrated that the predominant sterol of C. krusei is ergosterol and that fluconazole inhibits 14alpha-demethylase in this organism. The 14alpha-demethylase activity in cell extracts of C. krusei was 16- to 46-fold more resistant to inhibition by fluconazole than was 14alpha-demethylase activity in cell extracts of two fluconazole-susceptible strains of Candida albicans. Comparing the carbon monoxide difference spectra of microsomes from C. krusei with those of microsomes from C. albicans indicated that the total cytochrome P-450 content of C. krusei is similar to that of C. albicans. The Soret absorption maximum in these spectra was located at 448 nm for C. krusei and at 450 nm for C. albicans. Finally, the fluconazole accumulation of two of the C. krusei isolates was similar to if not greater than that of C. albicans. Thus, there are significant qualitative differences between the 14alpha-demethylase of C. albicans and C. krusei. In addition, fluconazole resistance in these strains of C. krusei appears to be mediated predominantly by a reduced susceptibility of 14alpha-demethylase to inhibition by this drug.

Antifungal Agents↗
PubMed1993

Anterior occipital cervical reconstruction with a free vascularized osteocutaneous graft: a case report.

Free vascularized osteocutaneous bone grafts are an unusual but effective method to reconstruct complex and extensive defects of skin and bone of the extremities due to trauma, tumor, or infections. Many recent publications support their utility in these situations. In distinction, little literature exists to document the use of free vascularized osteocutaneous flaps in the spine. This is likely due to the infrequent occurrence of concomitant skin and osseous defects that are not manageable by routine spinal and plastic surgical approaches. We recently managed a particularly challenging patient in whom six prior operations--three anterior and three posterior--to decompress and stabilize the occipital-cervical junction had failed. We used a free vascularized distal radius osteocutaneous flap for three purposes: to provide the patient with an optimal chance to obtain an extensive and critically important anterior occipital-cervical arthrodesis, to supply a stable soft tissue envelope for protection of a tenuous dural repair, and to reconstruct an atrophic and scarred posterior pharyngeal wall. We are unaware of any report to date that documents the use of a graft of this type in the spine. We wrote this brief article to document the indications for this operation, to illustrate the problems we encountered in this difficult reconstructive situation, and to report on the progress of our patient to date.

Adolescent↗
PubMed1986

Modified great toe wrap for thumb reconstruction.

Reconstruction of the traumatically amputated thumb can be achieved with good cosmetic and functional results utilizing autogenous bone graft and a neurosensory free wrap-around flap from the great toe. The donor area of the toe is modified to create a wrap-around flap to transfer innervated glabrous skin from the medial and lateral borders of the toe. This modification includes nail and nail matrix while preserving toe length and the important plantar weight-bearing skin of the great toe. A series of three patients who have undergone thumb reconstruction utilizing this method are reported. Postoperative follow-up averages 15 months. Sensory recovery is comparable to that reported in the literature; cosmetic appearance of the thumb and nail growth are good.

Adolescent↗
PubMed1985

Anatomic variations in the motor and sensory supply of the thumb.

Variations in the motor and sensory nerve supply to the thumb exist despite stereotyped descriptions in modern anatomy texts. A careful dissection of ten specimens under high magnification has been made with special reference to the nature and incidence of anatomic variations. Transligamentous passage of the recurrent motor branch of the median nerve was noted in six dissections; two of these included multiple motor branches to the thenar musculature. The Riche-Cannieu anastamosis was observed in three specimens. Variations in the branch pattern of the median nerve fibers supplying sensation to the thenar eminance and palmar thumb were also noted. No dorsal (superficial radial nerve) to palmar communications were detected, although this pattern has been described clinically. The differences give rise to an element of diagnostic uncertainty in treating the nerve-injured patient; functional deficits and therapeutic consequences are discussed in relation to the authors' observations and a review of the literature.

Humans↗