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Biomedical subjects

N A Williams

Publications and source records attributed to N A Williams.

At least 73 records · Page 4Linked to original sources

The in vitro production of cytokines by mucosal lymphocytes immunized by oral administration of keyhole limpet hemocyanin using cholera toxin as an adjuvant.

The in vitro production of a variety of cytokines by lymphocytes isolated from spleen mesenteric lymph node (MLN), Peyer's patches (PP) and lamina propria (LP) was measured, after oral immunization with keyhole limpet hemocyanin using cholera toxin as an adjuvant. LP responses were characterized by very high levels of interleukin (IL) 4, IL 5 and IL 6 with lower levels of IL 2 and interferon-gamma (IFN-gamma). The PP had lower levels of IL 4, IL 5 and IL 6 than LP but higher levels of IL 2, IFN-gamma was only present at very low levels in this organ. The MLN had a pattern of cytokine production similar to the PP but did produce IFN-gamma. The spleen produced all cytokines measured except IL 5. Antibody production was characterized by IgA in the LP and PP but IgG was the dominant isotype in the spleen, the MLN was a poor source of antibody-producing cells. We interpret the results to show that (a) the LP response to cholera toxin/keyhole limpet hemocyanin is dominated by Th2-type cytokines compared to a lower production of Th1 type and (b) that the PP has responses typical of an organ with a high proportion of resting lymphocytes which develop mainly into Th2-types cells. The spleen is less dominated by Th2-type cytokines than the mucosal sites and this difference is paralleled by IgA antibody production at the mucosal sites and IgG antibody dominance in the spleen.

Adjuvants, Immunologic↗

Effects on murine epidermal Langerhans cells of drugs known to cause recrudescent herpes simplex virus infection in a mouse model.

A number of agents have been shown to alter the latent state of herpes simplex virus in murine sensory ganglia. However, it seems that effective triggers of recrudescent disease must act not only to reactivate latent HSV infection, but also to create a favorable environment in the skin for viral replication. The possibility that alteration of the local Langerhans cell population is one way in which effective triggers of recrudescence may act has been investigated. Of the agents tested, which affect latent HSV, only DMSO significantly altered the numbers of ATPase-bearing Langerhans cells in the epidermis, maximally reducing their density by 83% in 48 h. Xylene and retinoic acid had no discernible effect on numbers of ATPase-staining cells over the 4 d tested. However, the extent to which agents reduced ATPase-staining cell numbers did not correlate with their ability to affect the antigen-presenting capacity of the cells in HSV-specific T-cell proliferative assays in vitro. Xylene and retinoic acid markedly reduced the accessory cell function of epidermal cell suspensions, whereas DMSO had no effect.

Adenosine Triphosphatases↗

Mucosal priming of T-lymphocyte responses to fed protein antigens using cholera toxin as an adjuvant.

Cholera toxin is widely recognized as a potent stimulator of mucosal IgA responses after oral feeding. However, comparatively little is known of its ability to stimulate cellular responses. This is due in part to the direct inhibitory effects of cholera toxin on T lymphocytes, which can confound attempts to study primed T-cell responses in vitro. We have avoided this problem by using cholera toxin as an adjuvant to enhance the response to an unrelated protein fed simultaneously. Thus the simultaneous feeding of 10 micrograms of cholera toxin and 5 mg of keyhole limpet haemocyanin (KLH) results in the priming of T cells in the spleen, mesenteric lymph nodes, Peyer's patch and lamina propria that proliferate when restimulated with KLH in vitro. The feeding of KLH alone does not result in such responses. Both CD4- and CD8-positive antigen-specific T cells were involved in the response and the cells produced both interleukins 2 and 4 on antigen restimulation in vitro.

Adjuvants, Immunologic↗

Murine epidermal antigen-presenting cells in primary and secondary T-cell proliferative responses to herpes simplex virus in vitro.

The role of epidermal Langerhans' cells in infection with herpes simplex virus (HSV) was investigated using a culture system that supports antigen-specific primary and secondary T-cell proliferative responses. Epidermal cell suspensions were capable of restimulating the response of in vivo primed T cells to UV-inactivated HSV. This capability was also present in cell suspensions enriched for Langerhans' cells, but was abrogated by the depletion of I-A-bearing cells. The magnitude, kinetics and phenotype of the responding cells were similar to those elicited when HSV was presented to primed T cells by antigen-presenting cells from the spleen. In marked contrast, whereas splenic antigen-presenting cells induced strong antigen-specific proliferation of unprimed T cells (primarily of the helper phenotype), Langerhans' cells failed to invoke any detectable reaction of such cells.

Animals↗

Conservation of engrailed-like homeobox sequences during vertebrate evolution.

The Drosophila melanogaster developmental gene engrailed (en) is a member of a distinct subfamily of homeobox genes with a wide phylogenetic distribution. Here we report the use of reduced stringency polymerase chain reaction (PCR) to amplify and clone 8 genes related to en from 5 vertebrate species, including representatives of the most ancient vertebrate lineages. Nucleotide and deduced amino acid sequence comparisons between mouse, toad, zebrafish, lamprey and hagfish genes reveal extensive evolutionary conservation, and suggests that 2 en-like genes have been retained in most vertebrate lineages.

Amino Acid Sequence↗

Murine epidermal antigen-presenting cells in primary and secondary T-cell proliferative responses to a soluble protein antigen in vitro.

The capacity of epidermal cells (EC) to present antigen to primed and non-immune T cells was investigated using a culture system that supports antigen-specific primary and secondary proliferative responses. Although both naive and bovine serum albumin (BSA)-immune T cells reacted against BSA in the presence of either splenic or epidermal antigen-presenting cells (APC), important differences were noted in the kinetics and the magnitudes of the various responses. Most conspicuous was the relatively poor primary response supported by EC which evidently elicited very few BSA-immune T-helper cells. Despite this, the primed antigen-specific T cells recovered were phenotypically similar to those resulting from the stronger primary responses induced by spleen cells. In contrast to this disparity in the ability to prime, EC and spleen cells stimulated secondary reactions of comparable magnitude. We therefore consider that, in comparison with splenic APC, EC may require some additional stimulus to acquire the capacity to prime.

Animals↗

The estimation of solubility in binary solvents: application of the reduced 3-suffix solubility equation to ethanol-water mixtures.

The reduced 3-suffix solubility equation (R3SSE) is applied to the characterization of solubility in the ethanol-water system. The data needed are the solubility of the compound in each of the pure solvents and at one ethanol-water composition. This composition has been estimated from solubility data to be 0.56 volume fraction of ethanol. The solubility obtained at this volume fraction is used to estimate the ternary solute-solvent interaction constant, C2. The R3SSE, with the C2 thus obtained, predicts the mixed solvent solubilities of the compounds tested, as accurately as that obtained from several volume fractions. The superiority of the R3SSE over two related equations--a simple second-degree polynomial equation and a simplified form of the R3SSE which neglects contributions to solubility from the solvent mixture--is also demonstrated for a number of solutes.

Caffeine↗

Topical ciclosporin for psoriasis: in vitro skin penetration and clinical study.

In contrast to oral administration, topical ciclosporin is not effective in the treatment of psoriasis. This may be due to the drug's inability to penetrate the stratum corneum or to a need for systemic metabolism of ciclosporin to active metabolites. We conducted a preliminary evaluation of the ability of ciclosporin, in a variety of vehicles, to penetrate excised human skin in a two-compartment diffusion cell, a standard in vitro technique for evaluating percutaneous drug delivery. A high-pressure liquid chromatography assay for ciclosporin did not detect the passage of ciclosporin through skin. This finding was consistent through multiple trials, some of which evaluated Azone or liposomal formulations, which are reported to enhance the penetrability of certain compounds. These results indicate that ciclosporin is unable to penetrate human skin in the vehicles tested. This may explain the lack of clinical efficacy we demonstrated in 5 patients with psoriasis treated with topical ciclosporin for 14-16 days.

Administration, Topical↗

Premenstrual syndrome research: using the NIMH guidelines.

The 1983 National Institute of Mental Health (NIMH) guidelines for a premenstrual syndrome (PMS) diagnosis were applied to Daily Rating Form (DRF) data in a prospective research study. The use of two sets of criteria, each consistent with the NIMH guidelines, resulted in prevalence rates of 44% and 17%. The authors discuss other problems in defining a "syndrome": symptom patterns and the relationship between PMS and the presence of a psychiatric disorder.

Adult↗

Excess free energy approach to the estimation of solubility in mixed solvent systems I: Theory.

An approach is developed by which the solubility of an organic compound in mixed solvents may be estimated. In this approach, an expression for the excess Gibbs free energy of mixing for multicomponent solvent systems was used to obtain parameters characteristic of the interaction between the solvents. A fairly simple equation which predicts the solubility of a solute in a binary solvent system over the entire solvent composition range was then derived. The equation may be partitioned into terms that contain (a) pure solvent solubilities, (b) solvent-solvent interaction contributions, and (c) contributions from the solute-mixed solvent interactions. The required data are the molar volume of the solute, the pure solvent solubilities, and, theoretically, one experimentally determined solubility in a solvent mixture. The equation can be easily extended for systems with three or more solvents.

Chemical Phenomena↗

Excess free energy approach to the estimation of solubility in mixed solvent systems II: Ethanol-water mixtures.

The use of the reduced three-suffix solubility equation in characterizing solubility in ethanol-water mixtures is discussed. The equation states that ln xs2,m = z1 ln xs2,1 + z3 ln xs2,3 - A1-3z1z3(2z1 - 1)- (q2/q1) + A3-12z21z3(q2/q3) + C2z1z3, where xs2,1, xs2,3, and xs2,m are the mole fraction solubilities of the solute in ethanol (subscript 1), water (subscript 3), and in the mixture (m); A1-3 and A3-1 are solvent-solvent interaction terms; C2 is a solute-solvent interaction term; and the q- and z-values are molar volumes and solute-free volume fractions, respectively. The contributions of the various terms in the equation to solubility are examined, and the possible use of its derivative in indicating whether a maximum may exist in the solubility profile is discussed. Methods of obtaining the solvent-solvent interaction constant and the ternary constant C2 are described, and the general effectiveness of the equation in describing solubility is examined. The equation is shown to be applicable to 10 compounds with widely different physical properties and, thus, appears to combine both ease of use and general utility.

Chemical Phenomena↗

Excess free energy approach to the estimation of solubility in mixed solvent systems III: Ethanol-propylene glycol-water mixtures.

The reduced three-suffix solubility equation derived from the Wohl excess free energy expression is used to describe the solubility of phenobarbital in propylene glycol-water, ethanol-propylene glycol, and ethanol-water-propylene glycol mixtures and the solubility of hydrocortisone in propylene glycol-water mixtures. Solvent-solvent interaction constants were obtained by fitting total vapor pressure versus composition data, obtained at 25 +/- 0.1 degrees C, to the Wohl excess free energy model for the solvents. The equation describes solubility in these systems satisfactorily except for phenobarbital in ethanol-propylene glycol, where the solubility is fairly high and assumptions involved in the derivation of the equation do not hold.

Chemical Phenomena↗

Life stress and chronic yeast infections.

This study investigated the relationships of positive and negative life change to yeast infections in women having a gynecological examination at a university health center. Subjects completed the Life Experiences Survey and a questionnaire about experiences with yeast infections and received, as a routine part of their visitation of the gynecology service, a standard gynecological examination, including a laboratory test for yeast infections. Positive life change was unrelated to any of the variables regarding yeast infections and was only minimally correlated with negative life change. Negative life change, while not related to the presence of current yeast infections, was positively correlated with the reported number of yeast infections during the past year, concern about these infections, and a number of physician visits for yeast infections. Negative life change was also negatively correlated with grade point average. Neither antibiotics nor contraceptive pill use interacted with negative life change to influence experiences with yeast infections.

Adolescent↗

The type material of the International Reference Centre for Avian Haematozoa.

The type, paratype, and reference material of avian hematozoa in the reference collection of the International Reference Centre for Avian Haematozoa is listed. This material includes one species of Atoxoplasma, 41 species of Haemoproteus, one species of Hepatozoon, two species of Lankesterella, 15 species of Leucocytozoon, 31 species of Plamodium, one species of Spirogregarina, and three species of Trypanosoma.

Animals↗

Blood parasites of some birds from Senegal.

A total of 809 birds from Senegal, including 43 species and 21 families, were examined for hematozoans; 93 birds (11.5%) harbored blood parasites, with only 7 (7.5%) harboring mixed infections. Species of Haemoproteus occurred in 81.7% of the infected birds while species of Plasmodium. Trypanosoma, microfilaria and Leucocytozoon were encountered less frequently. The majority of the sample was composed of species of ploceids and estrildidis and blood parasites were most prevalent in the colonial-nesting ploceids. Prevalence of blood parasites in Senegal was low in comparison to that seen in birds from other parts of Africa.

Animals↗

Avian hematozoa of some birds from Tchad.

A total of 389 birds of 32 species representing 14 families from Tchad were examined for blood parasites. Eighty-nine (22.9%) harbored infections of Haemoproteus (64%), Plasmodium (12.4%), Trypanosoma (1.1%), Atoxoplasma (=Lankesterella) (5.6%), and microfilaria (28.1%). Species of Leucocytozoon were not observed in the present study. The occurrence of the different genera differed markedly between bird families; members of the Ploceidae comprised 85% of the infected birds.

Animals↗