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Biomedical subjects

J McGhee

Publications and source records attributed to J McGhee.

At least 19 recordsLinked to original sources
PubMed2001

Safety and predictability of laser in situ keratomileusis enhancement by flap reelevation in high myopia.

PURPOSE: To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment following primary procedures for high myopia and astigmatism. SETTING: Corneal Diseases and Excimer Laser Research Unit, Department of Ophthalmology, University of Dundee, Dundee, United Kingdom. METHODS: This prospective observational study of retreatment comprised a cohort of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group (P < .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the stromal bed. RESULTS: The mean follow-up after retreatment was 12.8 +/- 5.1 months (range 1.5 to 24 months; 19 eyes >/=6 months, 13 eyes > or = 12 months). The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at 1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow-up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter statistically between 1 week and subsequent times. The mean UCVA improved from 6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%, 75.0%, and 95.8% of eyes, respectively. No significant complications that led to a loss of best corrected visual acuity were encountered, although retreatment procedures were more uncomfortable than primary procedures and self-limiting; epithelial ingrowth that did not threaten vision was common, and 2 patients complained of nighttime visual symptoms. CONCLUSIONS: Retreatment of residual myopia by reelevating the flap was relatively safe and predictable, with a low risk of sight-threatening complications. However, longer term studies may be required to detect late complications.

Adult↗
PubMed1999

Interleukin 12 and innate molecules for enhanced mucosal immunity.

Recent strategies for understanding the mechanisms underlying mucosal immune responses and subsequent development of mucosal vaccines for induction of targeted immunity now include cytokines and molecules of innate immunity. These studies have shown that cytokines influencing the development of T helper (Th) cells differentially affect the outcome of mucosal vs. systemic immune responses to mucosal vaccines. Serum antigen-specific antibody (Ab) responses were enhanced when either IL-6 or IL-12 was mucosally administered with a protein antigen, while only IL-12 induced antigen-specific mucosal IgA Ab responses. Mucosal IL-6 and IL-12 also affected the type of Th cell responses induced by CD4+ T cells from mice that received IL-12 secreted larger amounts of IFN-gamma and IL-6 when compared with mice nasally treated with IL-6. Discrepancies in the ability to enhance mucosal or systemic immune responses were also observed when human neutrophil peptide (HNP) defensins or lymphotactin were nasally coadministered with protein antigens. Only lymphotactin promoted mucosal secretory IgA (S-IgA) Ab responses while both lymphotactin and defensins enhanced systemic immunity to mucosally co-administered protein antigens. Mixed antigen-specific Th1 -and Th2-type CD4+ T cell responses were induced in the systemic compartment by both lymphotactin and the mixture of HNP-1, HNP-2, and HNP-3 defensins. However, HNPs failed to significantly enhance cytokine secretion by mucosally derived, antigen-specific CD4+ T cells relative to those isolated from the systemic compartment. In summary, these studies clearly show that IL-12 and lymphotactin are able to trigger S-IgA Ab responses and provide new avenues for the design of safe and targeted mucosal vaccines.

Adjuvants, Immunologic↗
PubMed1998

Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins.

This report describes a test of the hypothesis that the oncolytic effect of genetically engineered, replication competent herpes simplex viruses (HSV) depends both on cell destruction by the virus and an immune response to the tumor cells induced in an immunocompetent animal system. The oncolytic vector was a HSV recombinant virus in which both copies of the gamma 1 34.5 gene were replaced with the murine genes encoding the cytokine interleukin-4 (IL-4) or interleukin-10 (IL-10). The hypothesis predicted that if an immune response plays a role in survival following intratumoral treatment of tumor-bearing animals with HSV, expression of IL-4 should prolong survival whereas expression of IL-10 should reduce it. The results are that (1) these cytokines can be expressed by HSV in productively infected cells both in vitro and in vivo; (2) HSV-expressing IL-4 or IL-10 genes were able to infect and destroy glioma cells in vitro; (3) intracerebral inoculation of HSV expressing either IL-4 or IL-10 into syngeneic murine glioma GL-261 cells implanted in the brains of immunocompetent C57BL/6 mice produced dramatically opposite physiologic responses. The IL-4 HSV significantly prolonged survival of tumor bearers, whereas tumor-bearing mice that received the IL-10 HSV had a median survival that was identical to that of saline treated controls; (4) immunohistochemical analyses of mouse brains at 3 and 7 days after virus inoculation showed marked accumulation of inflammatory cells composed primarily of macrophages/microglia, with various proportions of CD8+ and CD4+ T cells, but few B lymphocytes. We conclude that the cytokines expressed from genes encoded in the viral genome influence HSV therapy of tumors and this is probably due to the host immune response. Thus, cytokine expression may be an important adjunct to tumor therapy utilizing genetically engineered HSV.

Animals↗
PubMed1998

Arginine enhances induction of T helper 1 and T helper 2 cytokine synthesis by Peyer's patch alpha beta T cells and antigen-specific mucosal immune response.

The effects of arginine on cell proliferation and subsequent T helper (Th) 1 and Th 2 cytokine synthesis by murine Peyer's patch (PP) Th cells in vitro and the influence of arginine on the induction of antigen-specific mucosal and systemic immune responses in vivo were examined. When the PP T cells were stimulated with the anti-alpha beta T cell receptor (TCR) antibody in the presence of different concentrations of arginine, a higher proliferative response was observed in the culture with an optimal concentration of arginine compared with that with a minimum amount of this amino acid. The concentration of cytokines in the supernatant, the number of cytokine-producing cells and the cytokine-specific mRNA expression of PP T cells were also increased in a dose-dependent fashion. Furthermore, when mice fed on an arginine-supplemented liquid diet were orally immunized with tetanus toxoid plus cholera toxin as a mucosal adjuvant, a higher level of antigen-specific fecal IgA was observed when compared with the response in mice fed on an arginine-free diet. Taken together, these results suggest that arginine enhanced antigen-specific mucosal immune response resulting from the supporting activation of cell proliferation and subsequent cytokine synthesis of PP Th cells.

Animal Feed↗
PubMed1996

Optimization of live oral Salmonella-HIV-1 vaccine vectors for the induction of HIV-specific mucosal and systemic immune responses.

Recent evidence suggests that live oral Salmonella-HIV vaccine vectors have the potential to elicit HIV-specific T cell-mediated immunity in both the mucosal and systemic compartments. We are using the mouse-typhoid model to identify Salmonella::HIV vaccine vector constructs that elicit HIV-specific mucosal and systemic immune responses. Oral immunization of mice with a Salmonella strain that expresses recombinant gp120 (rgp120) in the cytoplasm of the vector elicits a modest gp120-specific T cell proliferation response in the spleen. However, such Salmonella constructs did not stimulate the development of gp120-specific serum IgG or cytotoxic T lymphocytes (CTLs). Interestingly, the majority of cytoplasmically-expressed rgp120 forms inclusion bodies in Salmonella. We believe that in this form rgp120 is highly susceptible to protease degradation by the vector. As such, cytoplasmic rgp120 may not persist in the host after vaccination, resulting in the modest immunogenicity of rgp120 in these constructs. To circumvent this problem we constructed Salmonella strains that express rgp120 on the surface of the vector. Preliminary data suggest that surface-expressed rgp120 is significantly more immunogenic in both the mucosal and systemic compartments than cytoplasmic rgp120. These results, therefore, support the proposal that Salmonella vectors will be a safe and inexpensive means for delivery of HIV antigens to, and the elicitation of HIV-specific T cells in, the mucosal and systemic compartments.

Administration, Oral↗
PubMed1995

A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins.

We examined the capacity of a genetically detoxified derivative of pertussis toxin (PTX), PT-9K/129G, to act as a mucosal adjuvant for an intranasally (i.n.) administered tetanus vaccine. Groups of mice were immunized i.n. with the nontoxic C-terminal 50-kDa portion of tetanus toxin (fragment C [Frg C]) either alone or mixed with PT-9K/129G, PTX, or cholera toxin (CT) or were immunized subcutaneously (s.c.) with an equivalent amount of Frg C adsorbed to alhydrogel. In response to a single immunization, mice receiving Frg C plus PT-9K/129G or CT i.n. and parenterally immunized mice developed high-titer (> 20,000) anti-Frg C antibodies, whereas mice immunized i.n. with Frg C plus PTX or with Frg C alone seroconverted only after being boosted. The serum anti-Frg C response was dominated by immunoglobulin G1 (IgG1) in mice immunized with Frg C plus PT-9K/129G, with Frg C plus PTX, or s.c. In contrast, IgG1, IgG2a, and IgG2b contributed almost equally to the Frg C response when CT was the adjuvant. Anti-Frg C IgE was detected only in the sera of mice immunized i.n. with Frg C plus PTX and immunized s.c. with Frg C plus alhydrogel. High levels of IgA antibodies were present in nasal lavage fluid from mice immunized i.n. with Frg C plus PT-9K/129G, PTX, or CT but not in that from mice given Frg C alone i.n. or parenterally. The mucosal adjuvanticity of PT-9K/129G was manifested in inbred as well as outbred mice. A single i.n. dose of Frg C plus either PT-9K/129G or PTX (with high specific activity) was sufficient to protect all immunized mice from tetanus toxin challenge, in contrast to the case for mice that received Frg C alone i.n. We conclude that the pertussis toxin analog PT-9K/129G, which is devoid of ADP-ribosyltransferase activity, is a potent mucosal adjuvant for vaccines delivered via the respiratory tract.

Adjuvants, Immunologic↗
PubMed1991

Selection criteria for waste management processes in manned space missions.

Management of waste produced during manned space exploration missions will be an important function of advanced life support systems. Waste materials can be thrown away or recovered for reuse. The first approach relies totally on external supplies to replace depleted resources while the second approach regenerates resources internally. The selection of appropriate waste management processes will be based upon criteria which include mission and hardware characteristics as well as overall system considerations. Mission characteristics discussed include destination, duration, crew size, operating environment, and transportation costs. Hardware characteristics include power, mass and volume requirements as well as suitability for a given task. Overall system considerations are essential to assure optimization for the entire mission rather than for an individual system. For example, a waste management system designed for a short trip to the moon will probably not be the best one for an extended mission to Mars. The purpose of this paper is to develop a methodology to identify and compare viable waste management options for selection of an appropriate waste management system.

Ecological Systems, Closed↗
PubMed1990

Hyperostosis frontalis interna, acromegaly and hyperprolactinaemia.

The association between hyperostosis frontalis interna (HFI), acromegaly and hyperprolactinaemia was investigated. Thirty six acromegalic patients, of whom 19 had hyperprolactinaemia, were compared with 36 randomly-selected, age-sex matched controls. There was a higher prevalence of HFI in the skull X-rays of the acromegalic cohort (P = 0.0002) when compared to the control group. This difference was apparent in both men (P = 0.01) and women (P = 0.01). Acromegalic patients with hyperprolactinaemia also expressed HFI in a higher proportion of individuals than the control group (P = 0.0001). Intra- and interobserver variability was assessed and concordance with 100% and 97% in the moderate and severe HFI sub-groups. The following sub-group analysis was undertaken: acromegalics and those acromegalics with hyperprolactinaemia were compared with the controls and a highly significant distinction was confirmed (P = 0.0007 and P = 0.00001 respectively). A relationship between HFI severity and the patient's age was noted in both male and female acromegalics. Also, the severity of HFI appeared related to disease duration in female acromegalics. The cause of HFI remains unknown but appears to be strongly associated with acromegaly, particularly in the presence of co-existent hyperprolactinaemia. The association may have symptomatic significance and the presence of HFI should be confirmed or refuted in all patients with acromegaly.

Acromegaly↗
PubMed1985

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearance from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗
PubMed1971

Effects of actinobolin on growth and some metabolic activities of cariogenic streptococci in vitro and in vivo.

Actinobolin, a known inhibitor of protein synthesis, has been shown not to interfere selectively with acid production or dextransucrase activity in a cariogenic streptococcus when the antibiotic is added to a concentration of 500 mug/ml. It has also been shown that actinobolin does not alter the total in vivo flora of the oral cavity of the rat when tested in a rat caries model system. A culture of cariogenic streptococci, adapted to in vitro growth in the presence of 1 mg of actinobolin per ml, has also been isolated.

Animals↗
PubMedDate not supplied

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearence from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗