Swift action needed to close the skills gap in bioinformatics.
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Biomedical subjects
Publications and source records attributed to M MacLean.
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Recombinant ovine granulocyte/macrophage colony-stimulating factor (rOv GM-CSF) has been expressed in Chinese hamster ovary cells. A stable, cloned line of these cells has been established which secretes high levels (40 mu g ml(-1)) of rOv GM-CSF. Three murine monoclonal antibodies (mAbs) were produced which reacted with rOv GM-CSF on Western blots. These mAbs also neutralised the activity of both recombinant and native Ov GM-CSF in a bone marrow haemopoietic progenitor cell assay. Two of the mAbs, which recognise mutually exclusive epitopes, were selected for the development of a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GM-CSF in biological samples of ovine origin.
The local production of interferon-gamma (IFN-gamma) in sheep in response to Chlamydia psittaci was measured by cannulation of the efferent lymph duct draining the site of challenge inoculation. Peak production of IFN-gamma (256 U/ml) was detected 24 h after challenge. Based on these physiological data, functional studies were carried out in vitro to determine the effect of recombinant ovine (rOv) IFN-gamma on the multiplication of C. psittaci in ovine fibroblasts. IFN-gamma inhibited the multiplication of C. psittaci in ovine cells over a range of concentrations (250 U/ml to 2.5 U/ml) in a dose-dependent manner. The inhibition of chlamydial multiplication was most pronounced when cells were treated with rOvIFN-gamma for 24 h before infection. The addition of exogenous L-tryptophan (500 micrograms/ml) to cultures within 48th of infection abrogated the anti-chlamydial effect of rOvIFN-gamma thus suggesting that tryptophan deprivation is an anti-chlamydial mechanism induced by rOvIFN-gamma in these ovine cells.
24 preschool and 24 school-entry children in Bombay, India, and 24 preschool and 24 school-entry children in Oxford, England, were tested on their ability to distinguish between real and apparent emotion in response to stories involving child-adult and child-child interactions. Younger Indian girls did better than younger English girls, and the data reveal effects due to age, culture, gender, and story type which suggest a more social model of the understanding of emotion than has been proposed by other researchers using this methodology.
According to Communication Accommodation Theory, overaccommodation in intergenerational communication with elders is frequently based on stereotyped expectations of frailty and dependence. This study examined the role of nonverbal behaviors in such overaccommodation. Adult volunteers (N = 120; mean age = 29 years) read either a patronizing or neutral version of one of three conversations between a nursing home resident and a nurse. As in our earlier study, the nurse's use of the patronizing conversational style was rated as less respectful, less nurturant, and more frustrating for the resident than the neutral style. The main analyses indicated that negative nonverbal behaviors were rated as significantly more likely to occur with the patronizing style while positive nonverbal behaviors were rated as significantly less likely. The negative evaluative impact of patronizing style was especially apparent for instrumental task situations with high compliance demands. The effects for conversational style were essentially replicated for a smaller sample (N = 50) of formal care providers.
We describe the application of a novel filamentous phage vector system suitable for efficient screening and production of F(ab) antibody fragments. The vector system can concurrently produce free F(ab) fragments and F(ab) displayed on the surface of M13 bacteriophage via a VHCH1-pVIII fusion protein. When expressed in a supO (nonsuppressor) strain of Escherichia coli free F(ab) can be produced. Antibody F(ab) fragments are secreted into culture medium at concentrations up to 0.3 mg/liter and conveniently subjected to detailed analysis with little or no purification. Higher concentrations of F(ab) (approximately 10 mg/liter) were found to accumulate in the periplasmic space. In this report the vector system is shown to produce correctly folded and assembled F(ab) fragments of chimeric L6, a mAb against a tumor-associated Ag expressed by many human carcinomas.
OBJECTIVES: There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls. MEASUREMENTS: Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured. RESULTS: While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients. DISCUSSION: None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.
The prefemoral efferent lymphatics of four sheep persistently infected with a non cytopathic (NCP) isolate of border disease virus (BDV) were cannulated. Recovered lymphocytes were examined for the presence of virus by an immunocytochemical technique employing a pool of monoclonal antibodies which recognise the 120K non-structural polypeptide of NCP BDV. The results revealed that 9.5% of the lymphocytes carried virus antigen. Lymphocytes from two of the sheep were studied by in situ hybridisation using a viral antisense RNA probe complementary to the region of the BDV genome coding for the 120K polypeptide. This showed that 70-80% of the cells were infected, confirming the greater sensitivity of the in situ hybridisation technique.
Two experiments were carried out to determine whether expressive asymmetries in facial stimuli might underlie evidence of differential hemispheric responses to positive and negative emotion. Experiment 1 systematically varied stimulus orientation; Experiment 2 included both normally oriented and reversed (mirror-image) faces. We replicated previous reports of a left field advantage for happy faces and a right field superiority for sad faces only when normally oriented faces were used. Mirror-image stimuli tended to produce the opposite pattern of results, and a combination of the two (Exp. 2) eliminated the visual field differences for each emotion. The findings underscore the importance of controlling for stimulus asymmetries in visual laterality studies, and are discussed in terms of current notions about the lateralization of both the perception and expression of emotion.
Mouse monoclonal anti-idiotypic antibodies (anti-ids) were raised against L6, a murine IgG2a monoclonal antibody specific for a cell surface antigen expressed by many human carcinomas. Ten distinct anti-ids were generated. Eight anti-ids were shown to inhibit the binding of L6 to its target antigen and were characterized in detail. The heavy and light chain variable region gene segments of the monoclonal antibody L6 linked to human constant regions (chimeric L6) were expressed separately or together, to map the epitopes recognized by the anti-ids. Individual anti-ids were shown to recognize heavy chain, light chain, or combinatorial variable region determinants. Defining these specificities enabled us to select particular anti-ids for assays to monitor the pharmacokinetics of either murine or chimeric L6 antibodies in the circulation of human patients. A quantitative enzyme-linked immunosorbent assay developed with two anti-ids accurately detects less than 5 ng/ml. Anti-ids specific for light chain variable region-encoded determinants were capable of recognizing L6 antigen-binding fragments bound to the surface of human carcinoma cells. These anti-ids can be used to study the binding of chimeric L6 antibody at the surface of tumor cells in histological sections of tumor biopsies.
There is recent evidence that children naturally divide syllables into the opening consonant or consonant cluster (the onset) and the rest of the syllable (the rime). This suggests an explanation for the fact that preschool children are sensitive to rhyme, but often find tasks in which they have to isolate single phonemes extremely difficult. Words which rhyme share a common rime and thus can be categorized on that speech unit. Single phonemes on the other hand may only be part of one of these speech units. This analysis leads to some clear predictions. Young children, even children not yet able to read, should manage to categorize words on the basis of a single phoneme when the phoneme coincides with the word's onset ("cat," "cup") but not when it is only part of the rime ("cat," "pit"). They should find it easier to work out that two monosyllabic words have a common vowel which is not shared by another word when all three words end with the same consonant ("lip," "hop," "tip") but the odd word has a different rime than when the three words all start with the same consonant ("cap," "can," "cot") and thus all share the same onset. The hypothesis also suggests that children should be aware of single phonemes when these coincide with the onset before they learn to read. We tested these predictions in two studies of children aged 5, 6, and 7 years. The results clearly support these predictions.
This is a two-phase study. The first phase assesses the use of portable 2D echocardiography for diagnostic studies in remote areas. The second phase examines the diagnostic capabilities of 2D "only" versus 2D echocardiography combined with M-mode.
1. The ventilatory response to electrically induced ;exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to ;exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions.2. Phasic hind limb ;exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.3. Cord transection produced no significant change in either the resting values of ventilation ( V(I)) and CO(2) production ( V(CO) (2)) or the ventilatory equivalent for CO(2) during ;exercise' ( big up tri, open V(I)/ big up tri, open V(CO) (2)).4. During the steady state of exercise P(a, CO) (2) was on average significantly lower than at rest with the cord intact (mean big up tri, openP(a, CO) (2), - 2.1 mmHg; range - 5.7 to + 1), and higher, though not significantly, with the cord cut (mean P(a, CO) (2), + 1.2 mmHg; range - 1.5 to + 4.3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO(2) sensitivity; the big up tri, open V(I)/ big up tri, openP(a,CO) (2) obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO(2) inhalation (true sensitivity) both before and after cord section.5. V(I) and V(CO) (2) increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection.6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced ;exercise' was free of artifact.7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs.8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise.
1. The effect of electrically induced ;exercise' on the respiratory oscillation of arterial pH was studied in chloralose-anaesthetized dogs with spinal cord transection at T8/9 (dermatome level T6/7).2. Respiratory oscillations of arterial pH (presumed to be due to oscillations of arterial P(CO2)) were sensed with a fast-responding electrode in one carotid artery. Breath-by-breath estimates of the maximum rate of change of pH of the downstroke of the pH oscillation (dpH/dt downward arrowmax) were obtained by differentiating the pH signal.3. Consistent with the findings of the previous paper (Cross et al. 1982), the ventilatory response to exercise could not be explained on the basis of sensitivity to CO(2); the Delta V(I)/DeltaP(a, CO2) was significantly greater for ;exercise' than for CO(2) inhalation.4. On average, the amplitude of the pH oscillations decreased during ;exercise'. The change in the phase relationship (varphi) between respiratory and pH cycles, although significant from the second breath onwards, was not thought to be responsible for the increased ventilation V(I); the direction of the change was opposite to that previously found to increase V(I).5. Inspiratory duration (t(i)), expiratory duration (t(e)), V(I) and the dpH/dt downward arrowmax changed significantly by the third breath of ;exercise'. A significantly linear relationship was obtained between t(e) and dpH/dt downward arrowmax during the on-transient (first ten breaths) of ;exercise'. This relationship was maintained throughout ;exercise'. V(I) and dpH/dt downward arrowmax were also linearly related during the on-transient, although the same relationship did not hold true throughout ;exercise'.6. The dpH/dt downward arrowmax was related to CO(2) production ( V(CO2)) lending support to the prediction that the slope of the downstroke of the pH oscillation is a function of V(CO2).7. It was concluded that the dpH/dt downward arrowmax (dpCO(2)/dt upward arrowmax) is a potential humoral signal in ;exercise' and could account totally for the shortening of t(e). Since there was a late rise in V(I) (due to an increase in tidal volume V(T)) in the absence of a change in dpH/dt downward arrowmax, it was considered unlikely that the dpH/dt downward arrowmax was the only humoral signal present during ;exercise'.
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