Biomedical subjects
Publications and source records attributed to N MacLean.
A novel series of 5,5-diaryl-2-amino-4-pentenoates was synthesized and found to be potent and selective glycine transporter type-2 reuptake inhibitors.
N-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (Ki = 2.3 nM) relative to serotonin (Ki = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA2 = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists.
A novel series of 6-bicyclopiperazinyl-1-arylsulfonylindoles and 6-bicyclopiperidinyl-1-arylsulfonylindoles derivatives was synthesized and found to be potent and selective 5-HT6 receptor antagonists.
A series of 5-alkyltryptamines (6) and the corresponding conformationally constrained analogues (8) have been synthesized. The structure activity relationships (SAR) at the 5-position of the indole skeleton and the ethylamine side chain have been studied. Functional activities were assessed using isolated rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5-HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.
A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized, evaluated for their activity against the 5-HT2c and 5-HT2a, receptors and found to be agonists at 5-HT2c with selectivity over 5-HT2a.
OBJECTIVES: To compare outcome attributes of three available technologies for stem cell transplantation--bone marrow transplantation (BM), peripheral blood cell transplantation (PB), and cord blood transplantation (CB). To compare the cost per recipient for the three technologies, incorporating all donor and antigen matching functions, as well as the transplantation procedures. METHODS: Review of relevant literature using the CancerLit and HealthSTAR databases (plus earlier searches of MEDLINE and Embase) to summarize outcome differences. Estimations of cost per transplant using models drawing on Canadian experience. RESULTS: The literature review indicated that PB may have a modest advantage over BM in terms of outcomes. The literature indicated that CB has longer engraftment times (although this may be due to inadequate controls). Our modeling exercise indicated that costs for PB and BM are similar. CB has a higher cost per recipient, due in large part to the higher testing costs for every donated unit. CONCLUSIONS: Current literature is inadequate to provide an outcomes comparison of CB, PB, and BM. Viewed from a system-wide perspective, CB is a higher cost technique. However, PB and CB are emerging as technologies, and so our results should be viewed alongside the notion that there may be a steep learning curve in these technologies.
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Protein gene product (PGP) 9.5 is a developmentally regulated neuron- and neuroendocrine cell-specific ubiquitin carboxy-terminal hydrolase (UCHL1) expressed throughout the mammalian central and peripheral nervous systems. We have compared the use of monoclonal and polyclonal antibodies raised against human PGP9.5 for immunodetection of the protein in tissues of the zebrafish and rat. We show that a monoclonal antibody 13C4, which recognises an N-terminal epitope, detects PGP9.5 on Western blots as a single 27 kDa band present at high levels in zebrafish and rat brain. By contrast, the polyclonal antisera recognises multiple tissue-specific proteins in the rat and fails to detect PGP9.5 in the zebrafish. Finally, we have developed a specific ELISA assay for detection of cellular PGP9.5 using MAb13C4 and have employed the assay to show that PGP9.5 is not upregulated during nerve growth factor (NGF)-induced differentiation of rat PC12 cells.
The grain aphid Sitobion avenae (F.) was collected from winter wheat and adjacent cocksfoot grass at two locations in southern England and at four times in the year (April-July). Genetic variation between individual aphids was then investigated using random amplified polymorphic DNA polymerase chain reaction. Individuals caught in wheat and cocksfoot during April provided very different and highly diagnostic banding patterns that were independent of location. This host-based genetic differentiability was less evident as the season progressed, largely as a result of genetic drift and local movement between adjacent host species, which appeared to be predominantely in the direction from cocksfoot to wheat. The diversity of putative clones fell significantly, the mean number of individuals per clone rose and clones became more exclusively associated with certain sites which suggests that long-distance migration may have less of a homogenizing effect than hitherto thought for this species.
Samples of the grain aphid Sitobion avenae (F.) and the rose-grain aphid Metopolophium dirhodum (Walker) were collected in late March from wheat fields and adjacent road-side grasses at a number of locations in southern England. Unparasitized aphids were DNA fingerprinted using the multilocus (GATA)4 probe. Over all locations, the fingerprints of individual S. avenae caught in wheat had lower overall average distances of band migration (ADBM) and shared a higher proportion of bands, than fingerprints of individuals caught in adjacent road-side grasses. The ADBM of fingerprints of S. avenae collected on road-side grasses altered significantly with geographical location, while the ADBM of fingerprints of S. avenae caught on wheat did not. A comparison of the fingerprints of individual M. dirhodum caught in wheat and neighbouring road-side grasses did not reveal any genetic differentiation. Fingerprints of M. dirhodum that were caught in the same host type did however, show significant variation in ADBM between different locations. With both S. avenae and M. dirhodum, spatial autocorrelation revealed that locations that were close together were no more likely to have individuals with similar ADBM than locations that were far apart. Our results suggest that (i) particular clones of S. avenae prefer to colonize wheat, and/or that (ii) particular clones of S. avenae perform better on wheat than other clones. It is unclear why M. dirhodum did not show any genetic structuring according to host type, but this species appears to engage in sexual reproduction much more frequently than S. avenae in southern England.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND AND PURPOSE: The effect of using semirigid dressings (SRDs) on the residual limb of individuals who have had below-knee amputations as a consequence of peripheral vascular disease was investigated, with the primary question being: Does the time to readiness for prosthetic fitting for patients treated with the SRDs differ from that of patients treated with soft dressings? SUBJECTS: Forty patients entered the study and were alternately assigned to one of two groups. Nineteen patients were assigned to the SRD group, and 21 patients were assigned to the soft dressing group. METHODS: The time from surgery to readiness for prosthetic fitting was recorded for each patient. Kaplan-Meier survival curves were generated for each group, and the results were analyzed with the log-rank test. RESULTS: There was a difference between the two curves, and an examination of the curves suggests that the expected time to readiness for prosthetic fitting for patients treated with the SRDs would be less than half that of patients treated with soft dressings. CONCLUSION AND DISCUSSION: The results suggest that a patient may be ready for prosthetic fitting sooner if treated with SRDs instead of soft dressings.
Eleven independent transgenic canola (Brassica napus ssp. oleifera L. cv. Westar and Regent) lines were evaluated in the field. The plants carried a neomycin phosphotransferase (NPTII) gene for kanamycin resistance that was introduced via Agrobacterium-mediated transformation. NPTII enzyme assays, Southern blot by hybridizations and progeny analysis, confirmed the stable, heritable integration and expression of the introduced NPTII gene. A number of agronomic characteristics evaluated under field conditions, including maturity yield, and oil and protein content, were all statistically comparable between the transformed and nontransforemd platns. These results indicate that canola can be genetically engineered successfully, and that the Agrobacterium-based transformation system employed does not induced any adverse effects on the intrinsic agronomic and qualitative traits critical to the agricultural industry.
A review of Southland's perinatal mortality was undertaken from 1978 to 1983 and included 124 deaths with a postmortem rate of 90%. The perinatal mortality rate has continued to fall during this period, and has more than halved since 1971. Prematurity remains the single most important factor, and there are still a large number of avoidable deaths. Eighty percent of confinements are attended solely by general practitioner obstetricians.
The absence of centromeric bands in the karyotype of Felis catus is confirmed. It is also confirmed that no satellite band is visible in CsCl density gradients. However, a satellite is observed both by recentrifuging the fraction of the DNA that bands at high density in CsCl and by using netropsin to enhance the resolution of a CsCl gradient containing total F. catus DNA. The satellite, about 0.5% of total DNA, was isolated by repeated centrifugation in CsCl alone and in CsCl with netropsin. Netropsin was removed and a pure satellite DNA obtained. The reassociation kinetics (C0t1/2 less than 10(-3) M . s) show that the satellite is of the simple sequence type and hence a candidate for centromeric heterochromatin. Its cytological localisation awaits in situ hybridisation experiments.
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