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Biomedical subjects

C Stokes

Publications and source records attributed to C Stokes.

At least 19 recordsLinked to original sources
PubMed2006

Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior.

Cell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory-motor function. hNT-transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors.

Analysis of Variance↗
PubMed2006

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model.

Laryngeal transplantation is an increasingly viable proposition for patients with irreversible diseases of the larynx. One human transplant has been performed successfully, but many questions remain before routine transplantation can begin. In order to measure the immunological changes in mismatched transplants, it is first necessary to know the immediate combined effects of ischaemia-reperfusion injury (IRI) plus the added insult of major surgery in a fully matched setting. We measured the changes in immunologically active mucosal cells following 3 h of cold ischaemia and 8 h of in situ reperfusion in a major histocompatibility complex (MHC)-matched minipig model (n = 4). Biopsies were prepared for quantitative, multiple-colour immunofluorescence histology. The number of immunologically active cells was significantly altered above (supraglottis) and below (subglottis) the vocal cords following transplantation and reperfusion (P < 0.05, P < 0.001, respectively). However, the direction of the change differed between the two subsites: cell numbers decreased post-transplant in the supraglottis and increased in the subglottis. Despite the statistical evidence for IRI, these changes were less than the large normal inter- and intrapig variation in cell counts. Therefore, the significance of IRI in exacerbating loss of function or rejection of a laryngeal allograft is open to question. Longer-term studies are required.

Animals↗
PubMed2005

The influence of environment on development of the mucosal immune system.

The mucosal immune system expresses active responses against pathogens and also tolerance against harmless food and commensal bacterial antigens. The mechanisms that determine which of these outcomes occur after recognition of antigens by T-cells are not clear. One possibility is that it is determined by the initial interaction between a dendritic and a naïve T-cell in organised lymphoid tissue. However, such organised structures are, evolutionarily, quite recent and the original immune system must have made appropriate responses in more diffuse immunological architecture; a second possibility is that the critical interaction is between primed T-cells and their environment, in the lamina propria of the intestine. The mucosal immune system of neonates is poorly developed and inefficient at expressing appropriate immune responses. Development is influenced by a range of environmental factors including maternally derived antigen or antibody and commensal flora and pathogens. The intestine is a complex immunological structure in which the immune system and the macro- and microenvironment interact.

Animals↗
PubMed2005

The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function.

The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and 'harmless' antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).

Animals↗
PubMed1999

Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.

Amino Acid Sequence↗
PubMed1999

The cytotoxicity and mode of action of 2,3,4-trisubstituted pyrroles and related derivatives in human Tmolt4 leukemia cells.

4-Carbethoxy-1-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybenzoyl)-3-(4-methoxyphenyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g., human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase alpha, RNA polymerases, nucleoside kinase and ribonucleoside reductase.

Animals↗
PubMed1998

Analysis of the immunological cross reactivities of 213 well characterized monoclonal antibodies with specificities against various leucocyte surface antigens of human and 11 animal species.

213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from human and 11 animal species were analyzed for reactivities against leucocytes from human and 15 different animal species. We found 77 mAbs (36%) to cross-react. Altogether, 217 cross reactions were registered out of 3195 possible combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II specificities. This study defined cross reactions on the following markers: CD1a, 1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43, 44, 45, 45R, 46, 49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7 and Cattle-WC1. In order to characterize the molecular weight (MW) of the corresponding cross reacting antigens, selected mAbs were used to immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens were in good agreement with the MWs of the homologous antigens. The followed strategy was found to be efficient and economical in defining new leucocyte antigen reactive mAbs.

Animals↗
PubMed1998

Summary of the first round analyses of the Second International Swine CD Workshop.

The reactivity of 176 monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, together with 19 internal standards, was analyzed by flow cytometry on 16 different cell types as a means of establishing the proper cell subset for later detailed clustering analyses. The exact CD subset reactivity of the 19 internal standard mAb had been characterized in the First International Swine CD Workshop. The flow cytometric analyses resulted in 40 data sets which were then subjected to statistical clustering using the Leukocyte Typing Database IV (LTDB4) software. As result of this work, 22 clusters were defined. After review of these results, panels of mAb from the defined first round clusters were assigned to cell subsets. The respective mAb in those first round clusters were then distributed to subset group researchers for further examination during the second round of the workshop.

Animals↗
PubMed1998

Activation of T cells from the intestinal lamina propria of the pig.

This study found CD4+ T cells present in leucocyte populations isolated from the lamina propria of the pig to be almost exclusively CD45RC-, consistent with their being highly differentiated by exposure to antigen. Following activation in vitro these cells up-regulated expression of IL-2R with similar kinetics to splenic CD4+ cells. However, while splenic cells progressively secreted IL-2 into cultures during the first 24 h, IL-2 was not detected in supernatants of lamina propria cells after 8 h. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed that this reflected a transcriptional difference: IL-2 transcripts were detected in cultures of splenic and lamina propria cells in the first few hours after activation but persisted only in splenic cells. In contrast, IL-4 transcripts were strongly expressed by activated lamina propria cells. Cell-cycle analysis demonstrated that fewer lamina propria CD4+ cells progressed into S-phase than did splenic CD4+ cells (26.0 11.1% and 45.0 11.3% respectively, P=0.011). Our results suggest that CD4+ T cells in these populations are differentiated effector cells whose potential for expansion may be dependent upon local factors. Such cells may be targets for immunoregulation by their local microenvironment.

Animals↗
PubMed1995

Developing an integrated public health information system for Missouri.

The Missouri Department of Health realized it had a problem with 67 different information systems that ran on different platforms and could not communicate with one another. A new, integrated information system, the Missouri Health Strategic Architectures and Information Cooperative (MOHSAIC) is being developed based on information engineering (IE). This article describes IE, the process of developing MOHSAIC, and some key lessons learned in developing the system. Some of the lessons learned include the importance of executive sponsorship, tension between efficiency and program accountability, importance of confidentiality, and difficulties of funding an integrated system. The article stresses how integrated information systems will be important for the viability of public health under health care reform.

Computer Communication Networks↗
PubMed1995

Comparison of the requirement of porcine peripheral blood monocytes and intestinal lamina propria macrophages as accessory cells in primary allogeneic mixed leukocyte responses and oxidative mitogenesis.

Differences and/or similarities of the accessory cell activity of circulating peripheral blood monocytes (PBM) and intestinal lamina propria macrophages (LPM) in the pig have never been evaluated. Therefore this study was designed to compare the accessory cell activity of these cells in the induction of primary allogeneic mixed leukocyte responses (MLR) and polyclonal mitogenesis. Splenic adherent cells (SPAC) were used as control accessory cells. It was observed that PBM, LPM and SPAC induced significant T cell proliferation in response to allo-antigens. Significantly higher responses were elicited by SPAC, followed by PBM whereas, LPM induced low responses when cultures were established a T cell: accessory cell ratio of 1:1. PBM was the only accessory cell which induced significant responses at a cell ratio of 10:1. Whereas LPM and SPAC were able to induce significant oxidative mitogenesis, PBM were poor stimulators of this response. The observed difference between PBM, SPAC and LPM is attributed partly to differences in number of major histocompatibility complex (MHC) class II positive cells and the intensity of expression of the glycoproteins.

Animals↗
PubMed1994

The accessory cell activity of porcine intestinal macrophages in the induction of T cell responses.

Although intestinal macrophages stimulated significant T cell responses to MHC class II antigens and polyclonalmitogens, they were weak stimulators of ovalbumin-driven responses. These cells showed numerous and large endocytic vacuoles, lysosomes and phagolysosomes which may be indicative of active phagocytosis during the isolation process. The poor antigen presenting activity of the cells in protein antigen-elicited may be an in vitro artifact attributed to acquired inefficiency in antigen uptake and/or processing.

Animals↗
PubMed1992

The delayed-emesis syndrome from cisplatin: phase III evaluation of ondansetron versus placebo.

Cisplatin may evoke both an acute emetic response during the first 24 hours following treatment and a less well-recognized syndrome of delayed emesis. While delayed emesis is usually less severe in terms of frequency of vomiting episodes, the problem continues to result in significant morbidity. In comparison with acute emesis, the exact pathogenesis of the delayed emesis syndrome remains unclear. Although a combination of oral metoclopramide and dexamethasone is effective in many patients in preventing delayed emesis, almost 50% continue to experience at least one emetic episode when treated with this regimen. A phase III multicenter study has evaluated oral ondansetron versus placebo in the prevention of the delayed-emesis syndrome in 50 patients during days 2 through 5 following high-dose cisplatin administration. Although the daily rates of complete emetic control, failure, and control of nausea favor ondansetron, this trial is statistically inconclusive in establishing efficacy of ondansetron as a single agent in the prevention of delayed emesis. Ondansetron was well tolerated in the dose and schedule used.

Adult↗
PubMed1990

Commercial and naturally occurring fly parasitoids (Hymenoptera: Pteromalidae) as biological control agents of stable flies and house flies (Diptera: Muscidae) on California dairies.

Filth fly parasites reared by commercial insectaries were released on two dairies (MO, DG) in southern California to determine their effect on populations of house flies, Musca domestica L., and stable flies, Stomoxys calcitrans (L.). Spalangia endius Walker, Muscidifurax raptorellus Kogan and Legner, and Muscidifurax zaraptor Kogan and Legner were released on the MO dairy from 1985 to 1987 in varying quantities. Parasitism by Muscidifurax zaraptor on the MO dairy was significantly higher (P less than 0.05) from the field-collected stable fly (4.4%) and house fly (12.5%) pupae, compared with a control dairy (0.1%, stable fly; 1.3%, house fly). Muscidifurax zaraptor, released from April through October during 1987 on the DG dairy (350,000 per month), was not recovered in a significantly higher proportion from either fly species relative to the corresponding control dairy. No specimens of Muscidifurax raptorellus were recovered from the MO dairy. Parasite treatments had no apparent effect on adult populations of either fly species or on overall parasitism rate of field-collected stable fly (16.8%, MO; 17.2%, DG) and house fly (23.3%, MO; 20.9%, DG) pupae. Spalangia spp. were the predominant parasites recovered from field-collected stable fly and house fly pupae on all four dairies. Sentinel house fly pupae placed in fly-breeding sites on both release dairies were parasitized at a significantly higher rate, as compared with sentinel pupae on control dairies. The generic composition of parasites emerging from sentinel house fly pupae was 20.6% Spalangia spp. and 73.2% Muscidifurax spp., whereas in field-collected house fly pupae, Spalangia spp. and Muscidifurax spp. constituted 74.3 and 19.6% of the parasites, respectively.

Animals↗