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Biomedical subjects

S MacMillan

Publications and source records attributed to S MacMillan.

18 recordsLinked to original sources
PubMed2001

Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD.

Proton magnetic resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated with severity of illness and response to acute (12 weeks) treatment with paroxetine. In this report, OCD symptoms improved markedly in an 8-year-old girl treated for 14 months with the selective serotonin reuptake inhibitor paroxetine (titrated from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after medication discontinuation. A striking decrease in caudate Glx was observed after 12 weeks of treatment which persisted after medication discontinuation. These data provide further support for a reversible glutamatergically mediated dysfunction of the caudate nucleus in OCD that may serve as a pathophysiological and treatment response marker.

Brain Chemistry↗
PubMed2001

Increased medial thalamic choline in pediatric obsessive-compulsive disorder as detected by quantitative in vivo spectroscopic imaging.

The thalamus has been implicated in the pathophysiology of obsessive-compulsive disorder. Using a multislice spectroscopic imaging sequence, we reported reductions in right and left medial thalamic N-acetylaspartate/cytosolic choline + creatine/phosphocreatine and N-acetylaspartate/cytosolic choline levels in 11 pediatric patients with obsessive-compulsive disorder, 8 to 15 years, versus 11 case-matched healthy controls. These changes may reflect a change in N-acetylaspartate, cytosolic choline, or creatine concentrations. Therefore, using a validated phantom replacement methodology, we obtained absolute measures (mmol/L) of N-acetylaspartate, a putative marker of neuronal viability, cytosolic choline, and creatine in these subjects. A significant increase in cytosolic choline was observed in right and left medial but not lateral thalami in patients with obsessive-compulsive disorder versus controls. N-acetylaspartate and creatine did not differ significantly between case-control pairs in the medial or lateral thalamus. These findings provide new evidence of cytosolic choline abnormalities in the thalamus in pediatric obsessive-compulsive disorder.

Adolescent↗
PubMed2000

Feasibility of patient-collected vulval swabs for the diagnosis of Chlamydia trachomatis in a family planning clinic: a pilot study.

This pilot study set out to determine the feasibility of using patient-collected vulval swabs, instead of urine, for the diagnosis of female Chlamydia trachomatis infection. Main outcome measures included prevalence of infection and sensitivity, specificity, and acceptability of both test methods. An assessment was also made of those who declined to be tested. Consecutive women under 25 years of age attending a single urban family planning clinic were invited to participate. Sixty-eight percent (103/152) agreed to undergo testing. Overall prevalence was 11.7%. The sensitivity/specificity for the ligase chain reaction (LCR) assayed patient-collected vulval swabs and urine was 100%/100% and 92%/100%, respectively. The acceptability of self-collection was high with 93% characterising the test as 'not bad', 79% recommending it to a friend, and 79% choosing the test next time. Significantly more women, however, would choose urine for testing on a subsequent occasion (p < 0.001). Less than 1/5 of the patients who declined did not take part because of concerns regarding the vulval swab. Patient-collected vulval swabs assayed by LCR represent a non-invasive, sensitive, and acceptable way to detect genital C. trachomatis infection in women attending a family planning clinic. Compared with urine testing, benefits in terms of transport and processing should encourage more widespread use of this approach.

Adolescent↗
PubMed1998

Integrated YAC/STS physical and genetic map of 22.5 Mb of human Xq24-q26 at 56-kb inter-STS resolution.

A yeast artificial chromosome sequence-tagged site-based (YAC/STS) physical map of 22.5 Mb of the Xq24-q26 cytogenetic band region of the human X chromosome has been assembled. DNA coverage includes 857 large-insert clones formatted with 405 STSs to provide ninefold depth of DNA. At five points, no bridging clones have been recovered from 20 X-chromosome equivalents of human DNA in YACs or bacterial clones, but the placement of 25 ("CA")n polymorphic markers permits the ordering of contigs by comparison with the genetic linkage map and radiation hybrid data. The map localizes the X3000 translocation breakpoint and six genes (ANT2, NDUFA1, LAMP2, OCRL, IGSF1, and HDGF) at better than 100-kb resolution. The relatively gene-poor nature of the region is consistent with relatively low uniform 34-42% GC content in STSs across nearly all of the region.

Chromosome Breakage↗
PubMed1998

YAC/STS map of 15Mb of Xp21.3-p11.3, at 100kb resolution, with refined comparisons of genetic distances and DMD structure.

The 15 Mb region between DXS997 and DXS8054 in Xp21.3-p11.3 has been mapped at seven-fold average coverage in yeast artificial chromosomes (YACs) and 100 kb inter-sequence tagged site (STS) distance. YACs from six different collections show self-consistent maps. The STSs include 18 (CA) repeat and one tetranucleotide repeat marker that detect polymorphism, as well as eight well-studied genes, a second site for MXS1 sequences, and three expressed sequence tags (ESTs). One of the ESTs maps to intron 7 of Duchenne muscular dystrophy, and seems to be a processed intronic sequence with a poly(A) tail.

Base Sequence↗
PubMed1997

4.5-Mb YAC STS contig at 50-kb resolution, spanning Xq25 deletions in two patients with lymphoproliferative syndrome.

Sequence-tagged site (STS) content mapping in yeast artificial chromosomes (YACs) was used to cover the region deleted in two patients affected with X-linked lymphoproliferative disorder. The order of markers includes, centromere to telomere, DXS8009-DXS1206-DXS8078-DXS8044-DXS982- DXS6811-DXS8093-AFM240xblO- DXS75-DXS737-DXS100-DXS6-DXS1046-DXS803 8. The order of six major markers is confirmed by fluorescent in situ hybridization, and all the markers assigned by linkage mapping fall within a 1.6-cM interval. The contig comprises 90 clones containing 89 STSs, yielding a resolution of 50 kb; DNA in a gap just telomeric to DXS8044 has not been found in > 20 equivalents of YACs or bacterial clones. The two deletions were found to have centromeric breakpoints that lie close to DXS1206 and may be identical; the telomeric breakpoints are -150 kb apart, one falling between DXS737 and DXS100, the other between DXS100 and DXS1046. Several STSs near the breakpoints show weak amplification from more than one site; one gives products from three groups of YACs, and lie, respectively, within 50 kb of the centromeric and the two telomeric deletion borders. Such partially duplicated segments of DNA are candidates for involvement in the formation of the deletions.

Chromosome Deletion↗
PubMed1997

X chromosome map at 75-kb STS resolution, revealing extremes of recombination and GC content.

A YAC/STS map of the X chromosome has reached an inter-STS resolution of 75 kb. The map density is sufficient to provide YACs or other large-insert clones that are cross-validated as sequencing substrates across the chromosome. Marker density also permits estimates of regional gene content and a detailed comparison of genetic and physical map distances. Five regions are detected with relatively high G + C, correlated with gene richness; and a 17-Mb region with very low recombination is revealed between the Xq13.3 [XIST] and Xq21.3 XY homology loci.

Base Composition↗
PubMed1996

YAC/STS map of 9 Mb of Xq26 at 100-kb resolution, localizing 6 ESTs, 6 genes, and 32 genetic markers.

To facilitate functional analysis of the Xq26 region, the physical map has been extended across 9 Mb with 192 YACs and markers including 90 STSs (sequence-tagged sites) and 50 hybridization probes. Six genes and six ESTs are localized. In addition, 32 markers that detect polymorphism permit an integration of physical with genetic linkage data. The localizations of eight uncloned disease genes are thereby delimited on the physical map. The data also suggest a possible gradient of recombination across the cytogenetic band, with little or no recombination reported in the centromeric 3.5-4 Mb.

Base Sequence↗
PubMed1996

Factors associated with shear bond strength of composite resin to human enamel.

The preparation of enamel surfaces before etching by removing 0.5 mm of surface tooth structure is common-place in modern restorative dentistry. This study was designed to measure and compare the shear bond strength of composite resin bonded to prepared and unprepared enamel using various proprietary bonding systems. The analysed results failed to show significant differences between the shear bond strengths of the prepared and unprepared enamel specimens. Conditioning enamel surfaces for 60 seconds using 2.5% nitric acid where the solution was allowed to desiccate, resulted in significantly lower bond strengths compared to the other regimes. A correlation of the etchant pH with the mean shear bond strength of the adhesive systems to enamel was observed. The surface topography of the etched enamel surfaces correlated moderately well with the bond strengths obtained.

Acid Etching, Dental↗
PubMed1994

Characterization of four human YAC libraries for clone size, chimerism and X chromosome sequence representation.

Four collections of human X-specific YACs, derived from human cells containing supernumerary X chromosomes or from somatic cell hybrids containing only X human DNA were characterized. In each collection, 80-85% of YAC strains contained a single X YAC. Five thousand YACs from the various libraries were sized, and cocloning was assessed in subsets by the fraction of YAC insert-ends with non-X sequences. Cocloning was substantial, ranging up to 50% for different collections; and in agreement with previous indications, in all libraries the larger the YACs, the higher the level of cocloning. In libraries made from human-hamster hybrid cells, expected numbers of clones were recovered by STS-based screening; but unexpectedly, the two collections from cells with 4 or 5 X chromosomes yielded numbers of YACs corresponding to an apparent content of only about two X equivalents. Thus it is possible that the DNA of inactive X chromosomes is poorly cloned into YACs, speculatively perhaps because of its specialized chromatin structure.

Animals↗
PubMed1988

Translational control in early sea urchin embryogenesis: initiation factor eIF4F stimulates protein synthesis in lysates from unfertilized eggs of Strongylocentrotus purpuratus.

We have used cell-free translation systems from unfertilized eggs and embryos of the sea urchin Strongylocentrotus purpuratus to analyze the mechanisms limiting protein synthesis in early embryogenesis. Unfertilized egg lysates supplemented with nuclease-treated reticulocyte lysate were stimulated 2-4-fold in incorporation of radioactive amino acid into protein. Thirty-minute zygote lysates supplemented in this way were not stimulated. These results suggested that a component limiting translation in the unfertilized egg lysate was provided by the nuclease-treated lysate and that this component was no longer limiting protein synthesis following fertilization. In view of these results, partially fractionated lysates and individual purified translational components from mammalian cells were tested for stimulation of the unfertilized egg lysate. A 1000000g supernatant devoid of ribosomal subunits also stimulated the unfertilized egg lysate. Thus, the stimulation was not due to the addition of active ribosomal subunits but to soluble elements in the reticulocyte lysate. Of the soluble components tested, only the cap-binding protein complex eIF4F caused a dramatic stimulation of the unfertilized egg lysate (2-3.5-fold). The 30-min zygote lysate was not stimulated by eIF4F or by any of the other components tested, supporting the hypothesis that a block in the translational machinery is removed at fertilization. A rabbit reticulocyte shift assay was used to analyze whether mRNA is limiting in early development. When unfertilized egg lysate was added to the shift assay, there was no shift in radioactivity from 43S to 80S complexes, indicating the unfertilized egg mRNA is not available for translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A phase I-II study of ifosfamide in combination with adriamycin in the treatment of adult soft tissue sarcoma.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.

Adolescent↗