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M R Allansmith

Publications and source records attributed to M R Allansmith.

At least 37 records · Page 2Linked to original sources
PubMed1990

Penetrating the conjunctival barrier. The role of molecular weight.

Dinitrophenyl (DNP) derivatives of various molecular weights were tested for their ability to elicit ocular anaphylaxis after topical application to the eye of immunized animals. Adult male Sprague-Dawley rats were immunized by intraperitoneal injection of DNP-Ascaris suum extracts and alum and were then skin-tested with DNP-bovine serum albumin on day 13 post-immunization to assess their sensitivity to the DNP hapten. On day 14, animals were challenged topically with DNP derivatives in one eye; PBS was applied to the contralateral, control eye. Animals were evaluated clinically, and ocular tissues were processed for histologic evaluation. The compounds used for topical ocular challenge included the DNP derivative of egg albumin (MW 43,500 D), soybean trypsin inhibitor (MW 20,080 D), insulin (MW 5733 D), B-chain insulin (MW 3496 D), and lysine (MW 478 D). Only di-DNP-lysine elicited clinical signs of redness, edema, and tearing and histologic evidence of mast cell degranulation. None of the other compounds, tested in solutions of either equal numbers of milligram per milliliter or equimolar concentrations, elicited ocular anaphylaxis after topical application. A compound of low molecular weight, less than 3496, is needed to elicit ocular anaphylaxis when applied topically.

Administration, Topical↗
PubMed1989

Conjunctival deposition of eosinophil granule major basic protein in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis.

To investigate the role of the eosinophil in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis, we assessed the presence of eosinophil granule major basic protein in conjunctival tissues by immunofluorescence. Biopsy specimens of conjunctiva were taken from nine patients with vernal keratoconjunctivitis, seven patients with giant papillary conjunctivitis, and five control subjects. We performed a masked semiquantitative assessment of immunofluorescence on sections from each specimen. The vernal keratoconjunctivitis and giant papillary conjunctivitis groups had significantly (P less than .05) more major basic protein deposition than controls. No significant correlation between severity of disease and degree of major basic protein deposition was found. We found extracellular eosinophil granules in one of three vernal keratoconjunctivitis specimens examined by transmission electron microscopy. Thus, eosinophil degranulation commonly occurs in vernal keratoconjunctivitis and giant papillary conjunctivitis with release of eosinophil granule major basic protein and presumably other toxic granule proteins onto affected tissues. These cationic proteins are potent cytotoxins and are able to stimulate mast cell degranulation.

Blood Proteins↗
PubMed1989

Ocular anaphylaxis induced in the rat by topical application of compound 48/80. Dose response and time course study.

In the present study we sought to develop a model of ocular anaphylaxis based on the topical application of compound 48/80 to the surface of the rat eye. Doses ranging from 50 to 1000 micrograms were found to produce graded edema of the conjunctiva and swelling of the lid. On histologic examination, 50 microns compound 48/80 produced no changes distinguishable from those in PBS-treated controls, 150 microns produced mild alterations, and 250, 500, and 1000 micrograms compound 48/80 produced a marked increase in degranulated mast cells and a mild influx of neutrophils. The time course of the response to 250 micrograms and 1000 micrograms of compound 48/80 was evaluated over a 72-h period. Both doses elicited epithelial damage. A mild reduction in the number of mast cell was seen at 6 h in rats receiving 250 or 1000 micrograms. The reduction persisted to 72 h in rats receiving 1000 micrograms. The number of neutrophils was increased at 1 and 6 h in eyes treated with 250 micrograms and at 1, 6, and 24 h in eyes treated with 1000 micrograms compound 48/80. The clinical and histologic changes induced by application of 250 micrograms compound 48/80 resemble those seen in patients with allergic conjunctivitis suggesting that a model of ocular anaphylaxis based on the topical application compound 48/80 will be clinically relevant and experimentally practical.

Administration, Topical↗
PubMed1989

Morphologic evidence that compound 48/80-challenged rat eyelid mast cells differ in their states of maximal degranulation.

To determine the uniformity of response by mast cells in the rat eyelid, doses of compound 48/80 ranging from 50 to 1,000 micrograms in a 10-microliters drop were applied to one eye of 30 male Sprague-Dawley rats. Phosphate-buffered saline (PBS) was applied to the other eye. Every mast cell was counted throughout microscopic slides of the tissue of the lower eyelids. Both the position and degree of degranulation of every mast cell in each slide were recorded on schematic representations of the lower eyelid. Before histologic examination, animals were observed for clinical signs of ocular anaphylaxis. Doses of 50 and 150 micrograms had no observable clinical effect. At greater doses, edema of the lids and conjunctiva increased with dose. Doses less than 250 micrograms had no significant effect on the number of mast cells or degree of degranulation. Doses of more than 250 micrograms induced degranulation in approximately 50% of the eyelid mast cells. The degree and pattern of degranulation did not change with doses greater than 250 micrograms. The morphology of degranulated mast cells treated with 1,000 or 250 micrograms of compound 48/80 was indistinguishable. We conclude that once maximal stimulation for degranulation is achieved, higher levels of compound 48/80 will not increase the level or change the type of degranulation. In addition, the maximal level of degranulation varies from one mast cell to the next. Mast cells in close proximity may differ markedly in their level of maximal degranulation, with responses ranging from no degranulation to severe degranulation with exocytosis.

Administration, Topical↗
PubMed1989

Characteristics of the cellular response of the rat conjunctiva to topically applied leukotriene B4.

Cellular events in the rat conjunctiva were studied at 1, 6 and 24 h following the topical application of leukotriene B4. A significant increase was noted in the number of eosinophils (p less than 0.01) and neutrophils (p less than 0.05) at 1 h and only in eosinophils at 6 h after leukotriene B4 application at the 2-micrograms dose. At the 200-ng dose, the eosinophil count was significantly elevated at 1 h only, and the number of neutrophils was not significantly changed at any time point. No significant increase in cell counts was observed at the 20-ng dose. In conclusion, certain doses of topically applied leukotriene B4 significantly increased the number of eosinophils and neutrophils in the rat conjunctiva.

Administration, Topical↗
PubMed1989

Response of rat conjunctival mast cells to multiple versus single applications of compound 48/80.

A single application of the mast cell secretagogue compound 48/80 to the surface of the rat eye induces significant histologic changes. Ocular anaphylaxis is usually the result of repeated, not single, exposures to allergenic substances. The response of conjunctival mast cells to repeated daily applications of compound 48/80 was, therefore, evaluated. Ninety rats received one dose of compound 48/80 or phosphate-buffered saline almost daily for 17 days. The frequency and degree of mast cell degranulation and the number of mast cells and other inflammatory cells in the subepithelial conjunctiva were determined histologically. The clinical response was most marked after one application of compound 48/80; repeated daily applications markedly reduced the clinical response. In eyes treated with multiple applications, 75% fewer mast cells were observable in the conjunctiva by light microscopy compared with phosphate-buffered saline treated eyes. Most mast cells were granulated; a few showed mild to moderate degranulation. Except for epithelial damage, no tissue injury was associated with multiple applications of compound 48/80. In contrast to conjunctivae subjected to a single application of compound 48/80, conjunctivae receiving multiple applications resembled that of phosphate-buffered saline controls.

Administration, Topical↗
PubMed1989

Immunologic effects of extended-wear contact lenses.

All worn contact lenses are coated with materials from the tear film and the environment. Antigens are included in this complex and ever-present coating on the front and back surfaces of the worn contact lens. These deposited materials lead to insult of the conjunctival surface that influences mucus production and conjunctival-related comfort in the wearing of contact lenses.

Antigens↗
PubMed1988

Inflammatory changes in conjunctival scrapings after allergen provocation in humans.

This study was performed to investigate the inflammatory changes occurring in the human conjunctiva at different time periods after allergen provocation. Twenty-three ryegrass-sensitive patients with allergic conjunctivitis (19 with hayfever and four with vernal conjunctivitis) were challenged by topical administration of ryegrass antigen to the eye. Allergen concentrations were increased in increments until an immediate ocular allergic reaction was elicited. Numbers of various inflammatory cells (neutrophils, eosinophils, lymphocytes, and monocytes) found in conjunctival scrapings were quantified and correlated with the clinical profile, total serum IgE, and serum IgE to Rye I antigen. Twenty minutes after some level of antigen topical challenge to the eye, all patients had ocular redness, tearing, and itching. Compared with findings in seven control subjects, significant inflammatory cells were found in the conjunctival scrapings of patients before challenge (p less than 0.05) and 20 minutes (p less than 0.001) and 6 hours (p less than 0.002) after effective challenge. Significant increases in neutrophils of patients occurred after 20 minutes (p less than 0.001), and in eosinophils at 6 hours (p less than 0.005), compared with values of control subjects. When each case was evaluated individually, nine of the 23 patients had highly evident inflammatory changes 6 hours after allergen provocation. The levels of total serum IgE and serum IgE to Rye I antigen of these nine patients did not differ significantly from the other patients in the study. Our data provide the first evidence in humans that significant inflammatory changes in conjunctival scrapings are present long after allergen exposure has ended.

Adolescent↗
PubMed1988

Ocular allergy.

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Conjunctivitis, Allergic↗
PubMed1988

T cell populations in the lacrimal gland during aging.

The present study examined the influence of age and gender on T cell populations in the lacrimal gland. Lacrimal (exorbital) glands were obtained from male and female rats at 19 days (pre-puberty), 9 weeks (adult) and 14 months (mid-life) of age and tissues were processed for T cell subset identification. In females, the density of total (W3/13+ and OX 19+), helper/inducer (W3/25+) and suppressor/cytotoxic (OX 8+) T cells underwent a significant increase in tissues from before, to after puberty. Following this rise, the density of all T cell populations decreased in glands from young adult to midlife females. This pattern of accumulation contrasted with the T cell profile presented by glands from males: T cell densities appeared unaffected from 19 days to 9 weeks of age, and then either declined (OX 19+, W3/25) or remained unchanged (W3/13+, OX 8+) in tissues of 14 month rats. An influence of gender on the distribution of T cells was also apparent if results were corrected for age-associated variations in lacrimal gland weight. Thus, the absolute number of all T cell populations rose dramatically in glands of both sexes from pre- to post-puberty. However, from 9 weeks to 14 months of age, the total content of W3/13+, OX 19+, W3/25+ and OX 8+ lymphocytes decreased 2-fold in glands of females, but did not vary in tissues of males. Of interest, the number of W3/25+ and OX 8+ cells was analagous in all age groups examined. Moreover, the combined total of W3/25+ and OX 8+ cells was greater than that of W3/13+ or OX 19+ cells at every age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Effects of topical pre-treatment with dexamethasone on the immediate and late phases of topically induced ocular anaphylaxis in the rat.

We tested the effects of pre-treatment with dexamethasone on topically induced ocular anaphylaxis in the rat. Rats were immunized with dinitrophenylated Ascaris suum extract and challenged with di-DNP-lysine. Dexamethasone was administered topically once (24, 6, or 1 h before challenge) or three times (6, 4, and 2 h before challenge). A single pre-treatment given at 24 or 6 h had no significant effect. A single pre-treatment 1 h before challenge reduced the extent of edema assessed histologically but not clinically, and had no significant effect on the eosinophil count in conjunctival tissue examined 6 h after challenge. Eyes pre-treated with dexamethasone 6, 4, and 2 h before challenge showed a significant reduction in conjunctival edema assessed histologically and clinically 1 h after challenge. In addition, 6 h after challenge the number of eosinophils was significantly reduced. We conclude that repeated pre-treatment with dexamethasone can suppress both the immediate phase and the cellular late phase of topically induced ocular anaphylaxis.

Administration, Topical↗
PubMed1988

Impact of aging and gender on the Ig-containing cell profile of the lacrimal gland.

The present study investigated the influence of age and gender on the number of IgA- and IgM-containing cells in the lacrimal gland. Tissues were obtained from male and female rats at 0.2 (infant), 0.6 (pre-pubertal), 1.3 (pubertal), 3 (adult), 8 (mid-life) and 17 (senescent) months of age, then processed for immunofluorescence microscopy. No IgA-containing cells could be detected in lacrimal glands from infant rats, but a significant accumulation had occurred by 0.6 months of age. The extent of this increase was gender-dependent: tissues from male rats had significantly higher IgA-positive cell densities than those of females. After 0.6 months of age, no further variations in the density of IgA-containing lymphocytes were observed in female gland. In contrast, male glands exhibited marked fluctuations in the density of IgA-containing lymphocytes during the time period spanning puberty (0.6----3 months). Of interest, the frequency distribution of IgA-containing cells in tissue sections was not uniform in rats older than 0.2 months. Correction of cell densities for age-related elevations in lacrimal gland weight demonstrated that the total accumulation of IgA-containing cells was both age- and gender-related. Highest cell numbers were attained at 3 months in females and 3 and 17 months in males. Moreover, at all assessed ages, the total IgA-containing cell number in glands of males was greater than, or equal to, that in tissues of females.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Attenuation of rat conjunctival response by repeated hapten applications.

Attenuation of the rat conjunctival response by repeated topical challenge with dinitrophenyl (DNP) hapten was demonstrated in our study. Adult rats were immunized by intraperitoneal injections of dinitrophenylated Ascaris suum extract (DNP-Asc) and alum. Serum levels of anti-DNP homocytotropic antibody were determined by passive cutaneous anaphylaxis in rats prepared with antibody 48 hours earlier. In other animals, topical challenge was performed by applying N,N'-di-2,4-DNP-L-lysine (di-DNP-lysine) in phosphate-buffered saline (PBS) to one eye; PBS alone was applied to the fellow eye. The degree of conjunctival reaction was assessed clinically, and ocular tissues were processed for histological evaluation. The intensity of the conjunctival reaction and extent of mast cell degranulation were significantly greater after one challenge with di-DNP-lysine than after multiple challenges. In the multiple-challenge group, the contralateral eye remained responsive to a single challenge with di-DNP-lysine. These results may have implications for therapeutic interventions in ocular anaphylaxis.

Anaphylaxis↗
PubMed1988

Late-phase reaction in topically induced ocular anaphylaxis in the rat.

A cellular late-phase reaction is described in a rat model of topically induced ocular anaphylaxis. Rats were immunized with dinitrophenylated Ascaris suum extract and alum and were tested for active cutaneous anaphylaxis on day 13. Rats with a strong skin test response were selected for ocular challenge with di-DNP-lysine. Macroscopic observation and histologic evaluation were performed at 1, 6, and 24 h. In rats showing a moderate macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 h; no significant increase in eosinophils, neutrophils or lymphocytes was found in the conjunctive of these animals. In rats showing a marked macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 and 6 h; the number of eosinophils was significantly increased at 1 and 6 h, and of neutrophils at 6 h only. At 24 h, neutrophil and eosinophil numbers returned to baseline levels. There was no macroscopic evidence of a late-phase response in either group of animals. Our results suggest that, in keeping with earlier observations in human skin, a strong early response to antigen is required for the development of a late-phase ocular response in the rat.

Administration, Topical↗
PubMed1988

Dark-staining bodies in the conjunctival epithelium of rats after multiple topical challenges with compound 48/80.

Over a 17-day period, 96 Sprague-Dawley rats received approximately daily topical applications of compound 48/80 to the ocular surface of one eye and phosphate-buffered saline (PBS) to the other eye. On histologic examination, dark-staining bodies appeared in the conjunctival epithelium in all 48/80-challenged eyes after day 3. These epithelial dark bodies (EDBs) rarely appeared in PBS-challenged or in single-dose 48/80-challenged tissues. The EDBs, between two and 15 per 30 fields at x 1000 under light microscopy, were limited to the conjunctiva near the fornix rather than near or over the tarsal plate. We hypothesize that these EDBs are associated with repeated application of secretagogue to the conjunctiva.

Administration, Topical↗
PubMed1988

The effect of aging on the secretory immune system of the eye.

The objective of the present study was to examine the influence of aging on the ocular secretory immune system of the eye. Levels of IgA and free secretory component (FSC) were measured in lacrimal glands and/or tears of 0.6, 1.3, 3, 8 and 17-month-old male and female rats. In addition, the FSC output of lacrimal tissue cultured in vitro was evaluated. During the period from 0.6 to 1.3 months of age, the content of tear IgA increased nine- and 13-fold in females and males, respectively. This rise was paralleled by changes in the concentration of tear FSC. Prior to the onset of puberty, FSC could be detected in only 7% of tear samples, whereas after pubertal maturation, tear FSC levels had attained adult concentrations. This tear FSC profile was similar to the age-related pattern of FSC output by lacrimal tissue incubated in vitro. Following puberty, tear IgA content continued to increase in both sexes until adulthood (3 months of age) and then plateaued in females from 8 to 17 months of age. In contrast, tear IgA in males appeared to stabilize from 3 to 8 months and then rose significantly to the highest levels at 17 months of age. This increase in males was also reflected in their lacrimal tissue: IgA content underwent a six-fold elevation from 3 to 17 months. Of interest is that the differential kinetics involved in tear IgA and FSC expression resulted in an age-associated decline in the FSC/IgA ratio from post-puberty to senescence. A striking finding in these studies was the persistence of a sexual dimorphism in the secretory immune system of the eye. After pubertal development, IgA and FSC levels were significantly higher in tears of males, compared to those of females, at all ages tested up to 17 months. These gender- and age-related variations in tear IgA and FSC amounts could not be accounted for by changes in either the volume of, or total protein content in, tears.

Aging↗
PubMed1987

Effect of multiple applications of compound 48/80 on mast cells of rat conjunctiva.

We sought to determine the effect on rat conjunctival mast cells of chronic exposure to a degranulating agent. Compound 48/80 (250 micrograms in 10 microliter) was applied daily to the ocular surface of rats for a total of 13 treatments administered in 17 days. A single application of compound 48/80 was given to rats for comparison. Four groups of animals (6 in each group) were evaluated 1 or 48 h after the last application of compound 48/80 in both chronic exposure and single exposure studies. Although a single exposure to compound 48/80 induced significant degranulation of mast cells in animals observed 1 h after treatment, no significant degranulation of mast cells was observed 1 h after the last dose of compound 48/80 was given to rats whose conjunctiva had been chronically exposed to this degranulating agent. Thus, multiple applications of compound 48/80 attenuated the mast cell response to compound 48/80. This acquired tolerance to compound 48/80 was reflected in the lessened clinical signs in rats receiving repeated applications compared with those given a single application.

Animals↗