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Biomedical subjects

C A Scott

Publications and source records attributed to C A Scott.

At least 55 records · Page 3Linked to original sources

CD8 enhances formation of stable T-cell receptor/MHC class I molecule complexes.

T-cell antigen receptors (TCR) generally interact with moderate affinity with the complex formed by major histocompatibility complex (MHC) molecules and foreign peptides. MHC/TCR recognition is followed by the generation of a signal to the T cell through a monomorphic multicomponent system that includes the CD3 complex and accessory molecules such as CD4 and CD8. The interaction between the extracellular domains of MHC and TCR molecules, and the interaction of MHC and CD4/CD8 molecules, have been considered to occur independently of one another. We report here that the affinity of CD8 dimers for MHC class I molecules is independent of haplotype and peptide content, and that the affinity of the TCR for its specific ligand is enhanced through a reduced 'off' rate in the presence of either CD8alpha alpha homo- or CD8alpha beta heterodimers. Moreover, CD8 seems to help recognition of the specific MHC-peptide complex either by guiding an energetically favourable docking of TCR onto MHC, or by inducing conformational changes in the MHC complex that can augment the TCR/MHC-peptide interaction. CD8 should therefore be considered as an active participant in the T-cell recognition complex, rather than simply as an accessory molecule.

Animals↗

Role of chain pairing for the production of functional soluble IA major histocompatibility complex class II molecules.

Structural studies of cellular receptor molecules involved in immune recognition require the production of large quantities of the extracellular domains of these glycoproteins. The murine major histocompatibility complex (MHC) class II-restricted response has been extensively studied by functional means, but the engineering and purification of the native, empty form of the most-studied murine MHC class II molecule, IA, has been difficult to achieve. IA molecules, which are the murine equivalent of human histocompatibility leukocyte antigen-DQ molecules, have a low efficiency of chain pairing, which results in poor transport to the cell surface and in the appearance of mixed isotype pairs. We have engineered soluble IA molecules whose pairing has been forced by the addition of leucine zipper peptide dimers at their COOH-terminus. The molecules are secreted "empty" into the extracellular medium and can be loaded with single peptide after purification. These IA molecules have been expressed in milligram quantity for crystallization as well as for activation of T cells and measurement of MHC class II-T cell receptor interactions.

Amino Acid Sequence↗

A longitudinal study of local and peripheral isotype/subclass antibodies in Dictyocaulus viviparus-infected calves.

Although infection with the bovine lungworm, Dictyocaulus viviparus, stimulates high levels of resistance, the mechanisms involved in immunity to this parasite remain poorly understood. In an attempt to address the possible role of antibody in protective immunity, a longitudinal study was carried out in which the levels of both local and peripheral parasite-specific IgG, IgG1, IgG2, IgM and IgA were measured by ELISA. Five calves were infected orally with ten third stage larvae per kilogram on days 0, 65 and 112. Three challenge controls remained uninfected until day 112. Peripheral responses were measured in serum collected weekly and local responses were measured in bronchoalveolar lavage fluid (BALF) collected pre-infection and on two occasions after each infection. After the secondary infection, there were increases in respiratory rates in all the calves, but four of five calves had no first stage larvae (L1) in their faeces, suggesting that the parasites reached the lungs but did not develop to patency. Respiratory rates remained within normal limits after the tertiary infection and there were no parasites in the lungs at postmortem. Locally, in BALF, levels of all the antibody isotypes/subclasses increased after the primary infection, then again after the secondary infection. The highest levels of antibody were detected after the tertiary infection, when the calves were fully immune. In contrast, serum antibody levels increased from day 21 after primary infection and rose again after secondary infection, but thereafter slowly declined, with no increases after tertiary infection. Our findings suggest that the local antibody response was important in the immune response to D. viviparus infections in calves.

Animals↗

Activation of the electrocorticogram by propofol during surgery for epilepsy.

Propofol is used widely during general anaesthesia but there has been concern that it may be implicated in provoking seizure activity. We have investigated the effects of low-dose propofol on the electrocorticogram of anaesthetized patients undergoing surgery for medically intractable epilepsy. During continuous peroperative recording of the electrocorticogram, propofol was administered in 25 mg increments until burst suppression occurred. Activation of the electrocorticogram occurred in 17 of 20 patients. There was an increase in mean spike frequency in 16, extension of spike distribution in 15 and polyphasia in 13 patients. The mean dose of propofol required to cause burst suppression was 88.2 (range 25-175) mg. We conclude that at low doses, propofol caused activation of the electrocorticogram in epileptic patients but at higher doses burst suppression was induced.

Adolescent↗

Evaluating a palliative care program: methodology and limitations.

The article describes an evaluation of a palliative care service in a regional and tertiary care facility. The service components are described. The four outcomes chosen for evaluation were: (a) symptom relief; (b) satisfaction with care for patients/families; (c) utilization of community resources; (d) good nursing morale and low staff stress. Quality of life was measured using a symptom distress scale; satisfaction using an adapted Kristjanson FAMCARE scale; community resources with opinion and satisfaction surveys; and staff morale and stress with the Maslach Bumout Inventory and Latack's Coping Questionnaire. Results showed that overall symptom distress was reduced. Patients/families were generally satisfied, with some areas needing attention. Physicians were generally satisfied and believed patients/families benefited from the psychosocial support, respite, and education/information. Nurses felt they had the time, energy, resources and support to give quality care.

Community Health Services↗

DNA flow cytometry and glial fibrillary acidic protein reactivity in pleomorphic adenomas of the salivary glands.

OBJECTIVE: To evaluate and correlate morphologic features, glial fibrillary acidic protein (GFAP) reactivity and DNA content parameters in 32 pleomorphic adenomas of the salivary glands. STUDY DESIGN: The adenomas were subclassified according to the proportion of stroma and type of stromal differentiation. DNA flow cytometry was carried out on paraffin-embedded material. GFAP reactivity was determined immunohistochemically and evaluated as the percentage of positive cells. Follow-up ranged from 17 to 71 months; no recurrences were observed. RESULTS: Seven cases were aneuploid, 10 peridiploid and 15 diploid. Nondiploid tumors had a significantly higher S-phase fraction. Nondiploid adenomas were significantly associated with a greater percentage of stroma, while S-phase fraction showed only a trend toward being higher in tumors with a greater quota of stroma. Ploidy type and S-phase fraction were unrelated to sex, age, tumor diameter or site. GFAP reactivity was unrelated to subtype or S-phase fraction; a higher frequency of diploid tumors was seen among cases with a greater number of reactive cells. CONCLUSION: Aneuploidy is present in a significant percentage of typical cases. It is unrelated to tumor bulk and appears to have no effect on recurrence as long as surgical excision is complete.

Adenoma, Pleomorphic↗

Effects of cis-platinum and luteinizing hormone releasing hormone analogues on rat spermatogenesis. A morphologic and flow cytometric study.

OBJECTIVE: To evaluate morphologically and flow cytometrically the effects of cis-platinum (cis-diaminedichloroplatinum [CDDP]) administered acutely and chronically with and without gonadotropin releasing hormone analogue (LRA) pretreatment on adult rats to verify the feasibility of protecting the spermatic epithelium before chemotherapy. STUDY DESIGN: Six groups of adult Wistar rats were studied: 2 were treated with an LD50 dose of CDDP in single and 2 in multiple administrations, 1 of each was pretreated with LRA and 1 LRA control and one untreated group were also evaluated. Relative frequency of spermatogenic phases, qualitative alterations, Johnsen's score and percentage of cells in each DNA region were determined. RESULTS: Acute CDDP treatment reduced spermatids, spermatozoa and haploid cells. Chronic CDDP treatment induced in some rats a reduction in tetraploid cells and in others an increase associated with morphologically abnormal spermatids and cells showing aberrant hypodiploid content in analogy to all chronic CDDP LRA-pretreated animals. CONCLUSION: Single-dose CDDP reduces spermatids by killing rapidly cycling spermatogonia and inducing alterations in maturation; in repeated doses, more marked reductions in spermatogonia are seen, followed by a compensatory proliferation of residual stem cells with generation of cells with an aberrant DNA content. These alterations are not prevented by LRA treatment sufficient to determine inhibition of serum testosterone levels.

Animals↗

Non-small cell lung cancer. Morphology and DNA flow cytometry.

OBJECTIVE: To correlate stage-related and histologic features of non-small cell lung cancer (NSCLC) with DNA flow cytometric parameters. STUDY DESIGN: The clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed. RESULTS: NSCLC were classified on the basis of their DI in diploid, peridiploid, hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid tumors. DI was significantly related to pleural infiltration, pT, histologic type and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a wide DI distribution, squamous carcinomas were mostly diploid, triploid or hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and hypertetraploid. The best combination of features able to predict disease relapse was pT plus pN plus grading and divergent differentiation. CONCLUSION: Many stage-related and histologic features are associated with particular DI classes, which vary in relation to the feature itself and, in some cases, regardless of classical methods of grading and histologic typing. DNA content analysis highlights greater biologic heterogeneity in NSCLC than evidenced morphologically.

Adult↗

An epidemiological study of Cryptosporidium parvum in two herds of adult beef cattle.

Prevalences of Cryptosporidium parvum oocysts in faeces and of isotype-specific anti-C. parvum antibodies in serum of apparently healthy adult cattle on two farms were determined. On Farm 1 cryptosporidial diarrhoea had been recorded in more than 80% of calves born over the previous 5 years, whereas on Farm 2 cryptosporidiosis had never been reported. No differences were demonstrated in oocyst excretion or presence of antibodies between the two farms. C. parvum oocysts were detected in 62.4% of faecal smears collected from a total of 553 apparently healthy adult cattle. Sucrose flotation was performed on a proportion of the faecal samples. This proved a more sensitive technique, detecting oocysts in 92% of the samples tested, and highlighting the insensitivity of direct smears for detecting oocysts. More than 90% of the cattle had specific anti-C. parvum IgG, IgG1, IgG2 and IgM antibodies and 58% specific anti-C. parvum IgA antibodies. Results suggest that asymptomatic adults may play an important role in the epidemiology of cryptosporidiosis in calves.

Animals↗

Trophic effects of essential fatty acids on pig skin.

The daily oral administration of 3 ml of two oils (So-5407 and So-1129) containing essential fatty acids (EFAs) for 16 weeks resulted in a transient increase in cell proliferative activity in the skin of female Large White pigs. The So-5407 oil contained 7% gamma-linolenic acid (GLA) whereas So-1129 was an oil of similar composition, but with no GLA. Hyperplasia of the epidermis was observed after the administration of both oils, and this was characterized by an increase in the size of the rete pegs. The maximum effect occurred at 4 weeks after the start of oil administration, at which time the number of viable cell layers had increased by a factor of approximately 1.5, and mean epidermal thickness (excluding the stratum corneum) was approximately 40% greater than that of the epidermis prior to oil administration. There was a marked increase in the labelling index (LI) of the basal cell layer of the epidermis in pigs receiving So-5407. Maximum LIs were quantified at 4 weeks after the start of administration and were 18.8 +/- 1.3% and 13.1 +/- 1.7% for pigs receiving So-5407 and So-1129, respectively. After this time the LI declined progressively and had returned to values within normal limits (P > 0.1) by 8 weeks after the start of administration of both oils. A similar pattern of change in the LI was seen in the follicular epithelium, although the peak values at 4 weeks after the start of oil administration of 12.2 +/- 1.8% and 10.8 +/- 0.9 for the groups receiving So-5407 and So-1129, respectively, were lower than in the epidermis. Labelled cells were also counted in the papillary dermis and maximum values were again seen at 4 weeks after the start of oil administration. Of the two oils, So-1129 had the greatest effect, with the number of labelled cells in the papillary dermis being a factor of three to four-fold higher than in skin prior to oil administration, between 2 and 12 weeks after the start of administration.

Animals↗

Description of posterior fossa syndrome in children after posterior fossa brain tumor surgery.

Brain tumors are the second most common malignancy in children less than 15 years of age and the most common solid tumor of childhood. Approximately 60% to 70% of pediatric brain tumors originate in the posterior fossa. Since 1989, the two hospitals that comprise the setting for this study have treated 121 children with posterior fossa brain tumors. A postoperative syndrome, labeled posterior fossa syndrome, has been identified in certain children. This syndrome involves a variety of signs and symptoms including mutism or speech disturbances, dysphagia, decreased motor movement, cranial nerve palsies and, emotional lability. These signs and symptoms develop from an average range of 24 to 107 hours after surgery and may take weeks to months to resolve. The exact etiology of the syndrome is unknown. The purpose of this retrospective medical records review of 19 children diagnosed with posterior fossa syndrome is to describe the symptoms of the syndrome. Early recognition of this syndrome could facilitate preventive and restorative patient care, prevent subsequent complications, decrease length of hospital stays, and promote patient and family understanding of and coping with the syndrome.

Adolescent↗

Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids.

PURPOSE: To evaluate the possible role of essential fatty acids, specifically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. METHODS AND MATERIALS: Skin sites on the flank of 22-25 kg female large white pigs were irradiated with either single or fractionated doses (20 F/28 days) of beta-rays from 22.5 mm diameter 90Sr/90Y plaques at a dose rate of approximately 3 Gy/min. Essential fatty acids were administered orally in the form of two 'active' oils, So-1100 and So-5407, which contained gamma-linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, both 4 weeks prior and 10-16 weeks after, or in the case of one single dose study, just for 10 weeks after irradiation. Control animals received a 'placebo' oil, So-1129, containing no gamma linolenic acid or eicosapentaenoic acid over similar time scales before and after irradiation. Acute and late skin reactions were assessed visually and the dose-related incidence of a specific reaction used to compare the effects of different treatment schedules. RESULTS: A reduction in the severity of both the early and late radiation reactions in the skin was only observed when 'active' oils were given over the time course of the expression of radiation damage. Prior treatment with oils did not modify the radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionated doses of beta-rays produced the most significant modification to the radiation reactions, effects consistent with dose modification factors between 1.06-1.24 for the acute reactions of bright red erythema and/or moist desquamation, and of 1.14-1.35 for the late reactions of dusky/mauve erythema and dermal necrosis. There was the strong suggestion of an effect produced by the 'placebo' oil, So-1129, after higher daily doses of oil. CONCLUSIONS: Essential fatty acids can modulate normal tissue reactions when given over the time when radiation damage is normally expressed. Dose modification factors suggest that a > or = 10% higher dose is required to produce the same level of normal tissue injury. Clinical application of selected essential fatty acids at appropriate doses may lead to a significant increase in the therapeutic gain in patients treated for cancer by radiotherapy.

Animals↗

Technical aspects of transvaginal ultrasound-guided follicular aspiration in cows.

A 7.5 MHz rectal transducer adapted for transvaginal use was compared with a human microcurvilinear 6 MHz transvaginal transducer for follicular aspiration in cows. Some of the problems encountered while developing an accurate and repeatable technique are discussed, including the preparation of the cow, and the selection of the needle and suction apparatus. Proficiency in the retrieval of oocytes was improved through practice. Four cows were aspirated on days 2 to 4, 9 to 12 and 15 to 16 after oestrus in two successive oestrous cycles. The initial recovery rates were poor (7 per cent) and the oocytes were of poor quality, being almost completely denuded. However, after five weeks' practice recovery rates of 41 per cent were achieved and the oocytes were suitable for in vitro maturation.

Animals↗

Ultrastructural identification of entorhinal cortical synapses in CA1 stratum lacunosum-moleculare of the rat.

The goal of the present study was to identify and characterize, at the electron microscopic level, the synapses formed by entorhinal cortical (EC) axons in the hippocampal CA1 stratum lacunosum-moleculare of the adult rat. Phaseolus vulgaris leucoagglutinin was ionotophoresed at various loci throughout the mediolateral and dorsoventral extent of the EC to label EC-CA1 synapses. Virtually all labeled synapses were asymmetric and axospinous. EC axons did not preferentially synapse with any particular type of dendritic spine; rather, EC axons formed synapses with the range of dendritic spine morphologies observed in CA1 s. lacunosum-moleculare. Spines with either perforated or nonperforated postsynaptic densities were contacted by EC axons. Occasionally both a labeled and an unlabeled axon synapsed on a single dendritic spine head. The data are discussed in relation to the morphology of other afferent systems synapsing in s. lacunosum-moleculare and to the physiology of the EC-CA1 system.

Animals↗

The effect of rainfall on tick challenge at Kyle Recreational Park, Zimbabwe.

The effect of rainfall pattern on tick challenge was investigated at Kyle Recreational Park, Zimbabwe, from 1991 to 1992 using drag and removal plot methods to sample environmental tick density. The abundance of adults and nymphs of the brown ear-tick Rhipicephalus appendiculatus and larvae of the bont tick Amblyomma hebraeum was positively correlated with monthly rainfall, whereas no relationship with rainfall was revealed for larval R. appendiculatus, adults of the red-legged tick R. evertsi, or larvae of the blue tick Boophilus decoloratus. A comparison between 1991 (490 mm rainfall) and the drought year of 1992 (161 mm) revealed significant differences in the abundance of R. appendiculatus, A. hebraeum, and B. decoloratus. During the wet season, R. appendiculatus adults were 2-3 times more numerous in the environment during the higher rainfall year of 1991. A. hebraeum larval abundance exhibited a similar pattern to that of R. appendiculatus adults, but B. decoloratus larvae were more abundant in the drought year of 1992 during both the wet and dry seasons. Comparable tick abundance data collected at Kyle during the above-average rainfall years of 1975-1977 (mean = 1029 mm) were compared with tick challenge during the below-average rainfall years of 1991-1992 (mean = 326 mm). In grassland sand habitat and all habitats combined R. appendiculatus adults, nymphs, and larvae were much more abundant during the high rainfall years. In contrast, larvae of B. decoloratus were more numerous during the drier years. A hebraeum larvae were also more abundant during the drier years. The strong positive correlation of adult R. appendiculatus abundance with rainfall and the coincidence of increased adult tick challenge with increased rainfall indicate that adult R. appendiculatus tick burden on hosts would be heaviest during the wet season and high rainfall years.

Animals↗

The modulation of radiation-induced damage to pig skin by essential fatty acids.

The ability of essential fatty acids (EFAs) to modulate radiation-induced normal tissue injury was assessed in pig skin. Female Large White pigs (approximately 25 Kg) received 3 ml/day orally of either an 'active' oil [So-1100, containing 9% gamma-linolenic acid (GLA)] or a 'placebo' oil (So-1129) for just 4 weeks before or for 4 weeks before and for 16 weeks after irradiation; localised irradiation of skin was with single doses of beta-rays from 22.5 mm diameter 90Sr/90Y plaques. The severity of the acute reaction, assessed in terms of erythema or moist desquamation, was significantly less in those pigs that received So-1100 both before and after irradiation, as compared with those receiving that oil only prior to irradiation and the 'placebo' groups. Dose modification factors (DMFs) of between 1.13-1.24 were obtained. A similar reduction in the severity of acute skin injury was seen in pigs receiving So-1100 for only 10 weeks after irradiation. Late skin damage, assessed in terms of late erythema or dermal necrosis, was also reduced with So-1100, with DMFs of 1.14-1.51. No such modification was observed if So-1100 was only administered for 4 weeks prior to irradiation. No adverse side-effects were apparent as a result of EFA administration. So-1100 may represent a safe and valuable method of increasing the therapeutic gain in radiotherapy.

Animals↗