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Biomedical subjects

S Buchanan

Publications and source records attributed to S Buchanan.

At least 19 recordsLinked to original sources

Functional neuroimaging with MEG: normative language profiles.

The reliability of language-specific brain activation profiles was assessed using Magnetoencephalography (MEG) in five experiments involving ninety-seven normal volunteers of both genders ranging in age from seven to eighty-four years. MEG data were analyzed with a fully automated method to eliminate subjective judgments in the process of deriving the activation profiles. Across all experiments, profiles were characterized by significant bilateral activity centered in the superior temporal gyrus, and in activity lateralized to the left middle temporal gyrus. These features were invariant across age, gender, variation in task characteristics, and mode of stimulus presentation. The absolute amount of activation, however, did decline with age in the auditory tasks. Moreover, contrary to the commonly held belief that left hemisphere dominance for language is greater in men than in women, our data revealed an opposite albeit a not consistently significant trend.

Adolescent↗

Comparative changes in plasma concentrations of progesterone, oestradiol and LH during the ovulatory cycle in a multiple ovulating male line and a single ovulating traditional line of turkeys.

The aim of this study was to compare the profile of circulating concentrations of LH, progesterone and oestradiol in a multiple ovulating male line with that of a single ovulating line of traditional turkeys. Plasma samples from seven traditional and 12 male-line turkeys were obtained every 3 h for 36 h. Male-line and traditional turkeys had single peaks of LH and progesterone that were of similar duration in both lines. The mean height of the plasma peaks of LH and progesterone were similar in the two lines and there was no detectable peak plasma oestrogen concentration. Mean plasma concentrations of LH and oestrogen were higher in single compared with multiple ovulating turkeys, whereas there were no differences in mean plasma progesterone concentrations. The results indicate that the multiple ovulation state in genetically selected high-growth lines of turkey may be the result of a correlated response in the steroidogenic capacity of ovarian tissue associated with low plasma concentrations of oestrogen rather than of a disturbance in the hormone profile of the ovulatory cycle.

Animals↗

Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor: dependence on the C-terminal tail.

The prostaglandin E2 (PGE2) EP4 subtype is one of four prostanoid receptors that use PGE2 as the preferred ligand. We have investigated the agonist-mediated regulation of EP4 using a multifaceted approach. Short-term (30 min) agonist challenge of recombinant EP4 expressed in human embryonic kidney 293 cells (EP4-HEK293 cells) with PGE2 (1 microM) resulted in the desensitization of intracellular cyclic AMP (cAMP) accumulation and a reduction in cell surface [3H]PGE2 specific binding sites. These events correlated with sequestration of EP4, as visualized by immunofluorescence confocal microscopy and phosphorylation, as shown by [32P]orthophosphate labeling of the receptor. Stimulation of protein kinase A activity in EP4-HEK293 cells (10 microM forskolin or 1 mM 8-bromo-cAMP) did not induce EP4 desensitization, sequestration, or phosphorylation. In contrast, stimulation of protein kinase C activity (100 nM phorbol 12-myristate 13-acetate) attenuated PGE2-induced adenylyl cyclase activity and increased EP4 phosphorylation, but did not induce sequestration or a reduction in [3H]PGE2 specific binding sites. EP4 receptors containing a third intracellular loop deletion [EP4 (del. 215-263)] or a carboxyl-terminal tail truncation [EP4 (del. 355)] of EP4 were used to demonstrate that the C-terminal tail governs sequestration as well as phosphorylation of the receptor.

Amino Acid Sequence↗

A prospective randomised concurrent comparison of the COBE Spectra Version 4.7, COBE Spectra Version 6 (auto PBSC) and Haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non-haematological malignancies.

A prospective study of the CD34+ cell collection efficiency of three cell separators was undertaken comparing the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study, all had received mobilising chemotherapy and daily G-CSF (5 microg/kg subcutaneously). The first leucapheresis was performed when the peripheral blood absolute CD34+ cell count was > or = 20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 min or two total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra Versions, as were the yields per unit volume of blood processed. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines.

Antigens, CD34↗

Ovarian steroid hormone production in a multiple ovulating male line and a single ovulating traditional line of turkeys.

Ovarian production of oestradiol and progesterone was investigated in a single ovulating traditional line and a multiple ovulating male line of turkeys. The oestradiol output from small follicles in response to LH stimulation and the aromatase activity of the residual ovary were also compared. The multiple hierarchy of follicles in the male line was shown to consist of a series of follicles of a similar size and stage of physiological maturation. The follicles of the traditional line produced significantly greater quantities of oestradiol than those of the male line. Impaired oestradiol production may have resulted in the lower plasma oestradiol concentration observed in the male line. There was no difference in follicular progesterone output between the traditional-line and male-line turkeys. The oestradiol output of whole small white follicles in response to LH stimulation was similar in the two lines and the depressed steroidogenesis of the male line was not changed. The aromatase activity of the small follicles was also lower in the male line, and there was no evidence that the male line ovary produced oestradiol in quantities proportional to its size. The results demonstrated that the hierarchy of follicles in the male line consisted of groups of follicles of similar mass and hormone output and indicated that selection for increased meat yield may have resulted in reduced ovarian steroidogenesis in male-line turkeys, in comparison with traditional, unselected turkeys.

Animals↗

Prospective randomised concurrent comparison of the COBE spectra version 4.7, COBE spectra version 6 (Auto PBSCtrade mark), and haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non haematological malignancies.

A prospective study of three cell separators was undertaken to compare the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study; all had received chemotherapy and daily G-CSF (5 microg/kg subcutaneously) up to and including the first day of leucapheresis. The first leucapheresis was performed on the first day the peripheral blood absolute CD34+ cell count was > or =20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 minutes or 2 total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra versions, as were the yields per unit volume of blood processed. The product volume was significantly higher with the COBE Spectra Version 4.7 compared to the other two machines. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines. The COBE Spectra Version 6 is particularly useful for patients with potentially poor peripheral venous access because of its increased interface stability.

Adult↗

Effects of food restriction or delayed photostimulation on ovarian follicle number, plasma oestradiol concentration and vaginal collagen content in male-line turkeys.

1. An experiment was conducted to test the hypothesis that severe food restriction throughout the onset of lay or delaying photostimulation by 5 weeks would decrease the number of ovarian hierarchical follicles in male-line turkeys. It was proposed that a decrease in the number of hierarchical follicles would lower plasma oestradiol concentration and be associated with higher vaginal collagen content and a lower propensity to prolapse of the oviduct. 2. Five weeks after photostimulation, neither restriction to 63% of ad libitum body weight nor delayed onset of photostimulation had any significant effect on follicle number, plasma oestradiol concentration or vaginal collagen content. 3. It was concluded that neither food restriction nor delayed photostimulation can be used to control the over-development of the ovarian hierarchy in male-line turkeys.

Animals↗

Development of the reproductive system in turkeys with a high or low susceptibility to prolapse of the oviduct.

Lines of turkeys selected for rapid growth and high meat yield have an increased incidence of prolapse of the oviduct compared with unselected or traditional strains of turkeys. The development of the reproductive system and changes in plasma estrogen concentrations were compared in sire line and traditional turkeys with the aim of identifying any morphological or hormonal differences that could be associated with the high incidence of prolapse in the male line. Four turkeys from each strain were killed weekly from 0 to 7 wk postphotostimulation, and samples from prolapsed birds were obtained from field cases. There were no differences in the rate of development of the ovary, oviduct, uterus, vagina, sphincter ani muscle, or muscular cord of the ventral ligament between the two strains that could predispose the sire line to prolapse. Histological investigation of the uterus, vagina, muscular cord of the ventral ligament, and sphincter ani muscle 5 wk postphotostimulation in traditional, sire line, and prolapsed sire line turkeys did not reveal any differences that could be associated with prolapse. No prelay peak in plasma estradiol concentration was observed in either strain, and there was no evidence to suggest that plasma estradiol was higher in the sire line compared with the traditional turkeys. It was concluded that prolapse of the oviduct in sire line turkeys was not associated with any anatomical abnormalities or high plasma estradiol during reproductive development.

Anal Canal↗

The relationships between vaginal collagen, plasma oestradiol and uterine prolapse in turkeys.

Uterine and vaginal collagen content and plasma oestradiol concentration were measured in traditional, male-line and prolapsed male-line turkeys to investigate the higher incidence of uterine prolapse in the male-line strain. The effect of exogenous oestradiol on vaginal collagen and plasma oestradiol was also tested in the traditional and male-line strains. Vaginal collagen was significantly lower in the male-line compared to the traditional-line, while it was lowest in prolapsed male-line turkeys. Plasma oestradiol concentration was higher in the traditional-line than the male-line. No difference in plasma oestradiol concentration was found between prolapsed and non-prolapsed male-line turkeys. Administration of oestradiol for 7 days significantly raised plasma oestradiol concentration but had no effect on vaginal collagen. Decreased vaginal collagen content was associated with uterine prolapse and may predispose the male-line strain to uterine prolapse. There was no evidence from these results to support an involvement of oestradiol in uterine prolapse in male-line turkeys.

Animals↗

Passive immunotherapy in advanced HIV infection and therapeutic plasmapheresis in asymptomatic HIV-positive individuals: a four-year clinical experience.

We have been treating patients with advanced HIV disease using passive immunotherapy (PIT). Earlier studies of PIT which have been published concerned relatively short periods of treatment: our study is by far the longest and reports also on the long-term effects of plasmapheresis on healthy HIV-infected individuals. Fifty-nine patients with an average CD4+ T-cell count of 55 per cu.mm. at baseline were transfused at monthly intervals with 500 ml of hyperimmune plasma. No disease progression or death occurred among the 8 asymptomatic patients under the treatment, which lasted for 36.25 months on average. Seven of the 15 ARC patients progressed to AIDS but none died in an average period of 25.9 months. Seven of the 36 symptomatic AIDS patients with advanced disease died in an average period of 19.6 months. PIT appears to be nontoxic and to have beneficial effects lasting at least four years under continuous treatment. It probably delays disease progression in ARC and AIDS patients, and almost certainly does so in asymptomatic late HIV infection with a very low CD4+ T-cell count. None of the 51 donors suffered adverse effects, nor did any progress to ARC or AIDS in an average period of 30.1 months. Their laboratory parameters indicated a nearly stable condition: in particular, their average CD4+ T-cell count rose from 478 to 498. The study of our plasma donors indicated that repeated and frequent plasma donation by asymptomatic HIV-infected individuals could delay disease progression, although further studies are needed to investigate this.

AIDS-Related Complex↗

Differential labelling of laminin alpha 2 in muscle and neural tissue of dy/dy mice: are there isoforms of the laminin alpha 2 chain?

Laminin alpha 2, a sub-unit of the basement membrane component laminin-2, is deficient in the dy/dy and allelic dy2 J/dy2 J mouse. It is also the defective protein in a proportion of children with congenital muscular dystrophy. Linkage and mutational analysis have established that this is a primary effect caused by defects in the LAMA2 gene. Laminin alpha 2 has previously been shown to be deficient in dy/dy skeletal muscle, peripheral nervous system and brain. We report here preliminary observations on differences in detection of laminin alpha 2 in muscle, peripheral nerves and brain of dy/dy mice using three, well characterized antibodies. In normal muscle laminin alpha 2 is localized to the basement membrane of the myofibres and the Schwann cells of peripheral nerves, whilst in adult brain it is only detected on blood vessels. Our results show that there is appreciable, but slightly reduced, expression of laminin alpha 2 in skeletal muscle of dy/dy mice but almost no detectable protein in the brain, peripheral nerve and spinal nerve roots. Our observations are at present unexplained but they raise the possibility for the first time that there may be different tissue specific isoforms of laminin alpha 2. Molecular characterization of possible differences responsible for our observations may aid the identification of the mutation in the dy/dy mouse and lead to a better understanding of the role and expression of laminin alpha 2 in pathological conditions.

Animals↗

Characterization of single-unit activity in the mediodorsal nucleus of the thalamus during expression of differential heart rate conditioning in the rabbit.

Much recent evidence has shown that the thalamic-prefrontal axis is involved in Pavlovian conditioning in rabbits. However, while single cell activity in the prefrontal cortex has been previously studied during classical conditioning in rabbits, that of its thalamic projection nucleus, the mediodorsal (MD) nucleus, has not. Consequently, in the present research we recorded neuronal activity from individual cells in MD during expression of conditioned bradycardia in rabbits that received differential Pavlovian conditioning in which tones served as conditioned stimuli and periorbital shock served as unconditioned stimuli. The pattern of firing in MD was similar to that evoked in the medial prefrontal cortex (mPFC). Of 84 cells sampled, approximately 35% showed CS-evoked activity. Ninety percent of these cells showed increases in activity, while the remainder were biphasic, showing an initial increase followed by a decrease. Also, like the mPFC, some cells showed initial increases, which declined during CS presentation, while others showed gradual increases which reached their maximum at CS offset. Also some cells were responsive to the CS+ and others to the CS-. Thus, MD cells, like mPFC cells, are somewhat heterogenous with regard to responding to conditional stimuli, although, unlike the mPFC, no strictly inhibitory cells were found.

Animals↗

Riga-Fedes syndrome: natal or neonatal teeth associated with tongue ulceration. Case report.

A case of natal teeth associated with traumatic ulceration to the ventral surface of the tongue (Riga-Fedes syndrome) in a four week old boy is presented. On radiographic examination, two teeth, present at birth, were found to be early erupted deciduous lower central incisors. A family history of natal teeth, all involving both lower deciduous central incisors associated with trauma to the tongue during suckling, was elicited. The ulceration healed over a period of four weeks using an innovative conservative treatment regime, involving the use of Stomahesive Wafer. Four months later the only sign of any previous pathosis was a fibrous scar on the ventral surface of the tongue.

Bandages↗

Differential effects of tetrodotoxin (TTX) and high external K+ on A and C fibre compound action potential peaks in frog sciatic nerve.

Monophasic compound action potentials were recorded from Rana sciatic nerves. Three distinct peaks were observed and designated A alpha, A delta and C. All peaks were abolished by replacement of the external medium with Na(+)-free solution. However, the C peak alone was unaffected by external application of 1 microM tetrodotoxin (TTX), both A peaks were completely suppressed. The C peak was also the most resistant to chronic depolarization caused by increased external K+. K+ (17.6 mM) solution reduced peak areas to 5 +/- 4, 27 +/- 11 and 63 +/- 14% of control for A alpha, A delta and C components. The C peak was therefore Na(+)-dependent, TTX-resistant and K(+)-depolarization resistant. These attributes are similar to those described for somatal TTX-resistant Na+ channels in other species. But, application of 1 microM TTX to a K(+)-depolarized nerve caused a further reduction in C peak area, suggestive of a voltage-dependent block by TTX similar to that reported for cardiac muscle Na+ channels.

Action Potentials↗