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Biomedical subjects

M Geraghty

Publications and source records attributed to M Geraghty.

16 recordsLinked to original sources

Regional cortical white matter reductions in velocardiofacial syndrome: a volumetric MRI analysis.

BACKGROUND: Velocardiofacial syndrome, caused by a microdeletion on chromosome 22q.11, is associated with craniofacial anomalies, cardiac defects, learning disabilities, and psychiatric disorders. To understand how the 22q.11 deletion affects brain development, this study examined gray and white matter volumes in major lobar brain regions of children with velocardiofacial syndrome relative to control subjects. METHODS: Subjects were ten children with velocardiofacial syndrome and ten age- and gender-matched unaffected children. Coronal images were acquired with a 3-D spoiled gradient echo series and partitioned into 124, 1.5-mm contiguous slices. A stereotaxic grid was used to subdivide brain tissue into cerebral lobes, which were segmented into gray, white, and CSF compartments using an algorithm based on intensity values and tissue boundaries. Nonparametric statistics were used to compare lobar volumes of gray and white matter. RESULTS: Analyses indicated that children with velocardiofacial syndrome had significantly smaller volumes in nonfrontal, but not frontal, lobar brain regions. Volume reductions affected nonfrontal white matter to a greater extent than nonfrontal gray matter. CONCLUSIONS: The presence of white matter reductions may be related to disturbances in myelination or axonal integrity in velocardiofacial syndrome. Further work is required to delineate the nature and extent of white matter anomalies, and to link them to variation in the neurocognitive and neuropsychiatric phenotype of velocardiofacial syndrome.

Adolescent↗

Synthesis and antimicrobial activity of copper(II) and manganese(II) alpha,omega-dicarboxylate complexes.

Copper(II) alpha,omega-dicarboxylate complexes of general formulae, [Cu(O2C(CH2)nCO2)].xH2O, [Cu(O2C(CH2)nCO2) (phen)2].xH2O and [Cu(O2C(CH2),CO2)(bipy)y].xH2O (n = 1-8; y = 1, 2; phen = 1,10-phenanthroline; bipy = 2,2'-bipyridine) were synthesised. These copper complexes, some related manganese(II) complexes and the metal-free ligands were screened in vitro for their ability to inhibit the growth of Candida albicans. Metal-free 1,10-phenanthroline and all of the copper(II) and manganese(II) phenanthroline complexes were potent growth inhibitors, with only one bipyridine complex, [Cu(O2C(CH2)CO2)(bipy)2].2H2O, having moderate activity. The remaining substances were effectively inactive. Complexes which were active against C. albicans also proved effective against C. glabratta, C. tropicalis and C. kreusi with the manganese complexes retaining superior activity. For the phenanthroline complexes the active drug species is thought to be the dication [M(phen)2(H2O)n]2+ (M = Cu, Mn). Escherichia coli and Staphylococcus aureus were resistant to all of the metal complexes and also to metal-free 1,10-phenanthroline. Only the copper phenanthroline complexes showed intermediate activity against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

X-linked adrenoleukodystrophy: genes, mutations, and phenotypes.

X-linked adrenoleukodystrophy (X-ALD) is a complex and perplexing neurodegenerative disorder. The metabolic abnormality, elevated levels of very long-chain fatty acids in tissues and plasma, and the biochemical defect, reduced peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity, are ubiquitous features of the disease. However, clinical manifestations are highly variable with regard to time of onset, site of initial pathology and rate of progression. In addition, the abnormal gene in X-ALD is not the gene for VLCS. Rather, it encodes a peroxisomal membrane protein with homology to the ATP-binding cassette (ABC) transmembrane transporter superfamily of proteins. The X-ALD protein (ALDP) is closely related to three other peroxisomal membrane ABC proteins. In this report we summarize all known X-ALD mutations and establish the lack of an X-ALD genotype/phenotype correlation. We compare the evolutionary relationships among peroxisomal ABC proteins, demonstrate that ALDP forms homodimers with itself and heterodimers with other peroxisomal ABC proteins and present cDNA complementation studies suggesting that the peroxisomal ABC proteins have overlapping functions. We also establish that there are at least two peroxisomal VLCS activities, one that is ALDP dependent and one that is ALDP independent. Finally, we discuss variable expression of the peroxisomal ABC proteins and ALDP independent VLCS in relation to the variable clinical presentations of X-ALD.

Adrenoleukodystrophy↗

Controlled trial of pharmacist intervention in general practice: the effect on prescribing costs.

BACKGROUND: It has been suggested that the employment of pharmacists in general practice might moderate the growth in prescribing costs. However, empirical evidence for this proposition has been lacking. We report the results of a controlled trial of pharmacist intervention in United Kingdom general practice. AIM: To determine whether intervention practices made savings relative to controls. METHOD: An evaluation of an initiative set up by Doncaster Health Authority. Eight practices agreed to take part and received intensive input from five pharmacists for one year (September 1996 to August 1997) at a cost of 163,000 Pounds. Changes in prescribing patterns were investigated by comparing these practices with eight individually matched controls for both the year of the intervention and the previous year. Prescribing data (PACTLINE) were used to assess these changes. The measures used to take account of differences in the populations of the practices included the ASTRO-PU for overall prescribing and the STAR-PU for prescribing in specific therapeutic areas. Differences between intervention and control practices were subjected to Wilcoxon matched-pairs, signed-ranks tests. RESULTS: The median (minimum to maximum) rise in prescribing costs per ASTRO-PU was 0.85 Pound (-1.95 Pounds to 2.05 Pounds) in the intervention practices compared with 2.55 Pounds (1.74 Pounds to 4.65 Pounds) in controls (P = 0.025). Had the cost growth of the intervention group been as high as that of the controls, their total prescribing expenditure would have been around 347,000 Pounds higher. CONCLUSION: This study suggests that the use of pharmacists did control prescribing expenditure sufficiently to offset their employment costs.

Community Pharmacy Services↗

Molecular characterization of Saccharomyces cerevisiae Delta3, Delta2-enoyl-CoA isomerase.

We report here the identification of the Saccharomyces cerevisiae peroxisomal Delta3,Delta2-enoyl-CoA isomerase, an enzyme that is essential for the beta-oxidation of unsaturated fatty acids. The yeast gene YLR284C was identified in an in silico screen for genes that contain an oleate response element, a transcription factor-binding site common to most fatty acid-induced genes. Growth on oleic acid resulted in a significant increase in YLR284C mRNA, demonstrating that it is indeed an oleate-induced gene. The deduced product of YLR284C contains a type 1 peroxisomal targeting signal-like sequence at its C terminus and localizes to the peroxisome in a PEX8-dependent manner. Removal of YLR284C from the S. cerevisiae genome eliminated growth on oleic acid, but had no effect on peroxisome biogenesis, indicating a role for YLR284C in fatty acid metabolism. Cells lacking YLR284C had no detectable Delta3,Delta2-enoyl-CoA isomerase activity, and a bacterially expressed form of this protein catalyzed the isomerization of 3-cis-octenoyl-CoA to 2-trans-octenoyl-CoA with a specific activity of 16 units/mg. We conclude that YLR284C encodes the yeast peroxisomal Delta3,Delta2-enoyl-CoA isomerase and propose a new name, ECI1, to reflect its enoyl-CoA isomerase activity.

Amino Acid Sequence↗

Mosaicism for trisomy 3q arising from an unbalanced, de novo t(3;15).

We report on a 2 1/2 year old girl who is dysmorphic, developmentally delayed, and mosaic for an unbalanced, de novo translocation between chromosomes 3 and 15. The karyotype from peripheral blood lymphocytes is 46,XX (50) and the karyotype from skin fibroblasts is 46,XX (28)/46,XX,der(15)t(3;15)(q11;p11) (23). The mechanism for the generation of this unbalanced, de novo translocation is discussed.

Abnormalities, Multiple↗

Tubulointerstitial nephritis in methylmalonic acidemia.

We report two patients with methylmalonic acidemia (MMA) in whom renal biopsy demonstrated interstitial nephritis, bringing the total of such reported cases to four. In addition, hypertension, observed in one of our patients, has not been previously reported as the presentation of renal disease in MMA. The etiology of interstitial nephritis in MMA did not appear to be due to urate nephropathy. To date, 15 patients with MMA have been reported with renal complications, including chronic renal failure, making it imperative that children with MMA have their renal status evaluated.

Amino Acid Metabolism, Inborn Errors↗

Sublocalization of the synovial sarcoma-associated t(X;18) chromosomal breakpoint in Xp11.2 using cosmid cloning and fluorescence in situ hybridization.

In a previous study we localized the synovial sarcoma-associated t(X;18)(p11;q11) breakpoint within the ornithine aminotransferase-like 1 (OATL1) cluster on the X chromosome. This localization was delineated from both somatic cell hybrid and fluorescence in situ hybridization (FISH) analysis of patient material, using OAT-specific cDNA and YAC probes. Simultaneously, Knight et al. (1992, Mol. Hum. Genet, in press) mapped this same breakpoint in their patient material adjacent to the more proximal OATL2 region on the X chromosome. Here we report the analysis of two additional tumors and demonstrate that again in these cases the chromosomal break occurs within the OATL1 cluster. In order to further specify the breakpoint, we subcloned the OATL1 YAC (no. 2) into cosmids. At least one of these cosmids (0.38) hybridizes to sequences that bracket the translocation breakpoint, as demonstrated by both Southern blot and FISH analysis. These observations confirm and substantiate our previous findings. In addition, cosmid 0.38 should be a valuable instrument for the ultimate isolation and identification of the gene(s) involved in the development of synovial sarcoma.

Animals↗

Monoribosomal attachment to messenger ribonucleic acid in sodium fluoride-treated rabbit reticulocytes.

Mild proteolysis with Pronase selectively dissociates ribosomes not attached to mRNA into subunits; ribosomes attached to mRNA remain intact. A portion of monoribosomes from reticulocytes incubated with NaF resisted proteolytic dissociation. Recovery of mRNA from monoribosomes of NaF-treated reticulocytes therefore may be explained by persistent attachment of some monoribosomes to mRNA.

Animals↗

Bacterial safety of reconstituted continuous drip tube feeding.

Chemically defined diets require reconstitution and transfer to a delivery system. When reconstituted High Vivonex was noted in our Medical Center to be bacteriologically contaminated, we instituted a series of control procedures. We then reevaluated bacterial growth in reconstituted High Nitrogen Vivonex and diluted Isocal under ward conditions. The mixtures were prepared with sterile water versus tap water, using a hand washed blender versus a machine washed blender. We also investigated the bacteriological effect of blast freezing reconstituted High Nitrogen Vivonex. All preparations of the nonfrozen High Nitrogen Vivonex showed occasional low level contamination, although quantitative cultures did not show logarithmic growth over eight hours of observation. No growth occurred in the blast frozen High Nitrogen Vivonex or in the Isocal. We conclude that reconstituted High Nitrogen Vivonex and diluted Isocal may be prepared and hung safely for eight hours, and that blast freezing of High Nitrogen Vivonex is bacteriologically safe. As a result of our initial findings of bacteriologic contamination, we believe a program for bacterial monitoring of the tube feeding is desirable.

Bacterial Infections↗