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Biomedical subjects

D W Richards

Publications and source records attributed to D W Richards.

At least 19 recordsLinked to original sources
PubMed1995

Characterization and identification of proteinases and proteinase inhibitors synthesized by temporomandibular joint disc cells.

The adult mammalian temporomandibular joint (TM) disc is a fibrocartilaginous tissue that undergoes normal developmental remodeling, requiring removal of the existing extracellular matrix and its replacement by new matrix macromolecules. This remodeling is probably mediated by matrix-degrading enzymes, but to date none has been demonstrated in association with the TMJ disc. We characterized, identified, and determined the regulation of proteinases and proteinase inhibitor (PIs) synthesized by TMJ disc cells in organ and cell cultures. TMJ discs were retrieved from 14-week-old male NZW rabbits and both tissue- and disc-derived cells were cultured in serum-free medium. The conditioned media were retrieved at 12-hour intervals and assayed for proteinases and PIs in gelatin- and casein-impregnated polyacrylamide gels. Three proteinases with gelatinolytic activities at 92 kDa, 72 kDa, and 42/57 kDa and one caseinolytic activity at 51/54 kDa were detected. All were inhibited by 1,10-1 phenanthroline, thus characterizing these enzymes as matrix metalloproteinases (MMPs), most likely 92-kDa gelatinase (proMMP-9), 72-kDa gelatinase (proMMP-2), procollagenase (proMMP-1), and prostromelysin (proMMP-3). The identity of the latter two MMPs was confirmed by Western blots. Two PIs and 30 kDa and 20 kDa, probably tissue inhibitors of metalloproteinase (TIMP) and TIMP-2, were observed on reverse zymograms. TPA, a protein kinase-C agonist, increased the expression of 92-kDa gelatinase and 30-kDa PI by both explanted discs and isolated disc cells. The profile of MMPs constitutively expressed by disc cells is similar to that of synovial fibroblasts but different from that of chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Detection of intraocular pressure change in the eye using sonoelastic Doppler ultrasound.

We report the first use of sonoelastic Doppler ultrasound for in vivo and in vitro clinical studies of intraocular pressure (IOP). The method involves low-amplitude and low-frequency sonic excitation of the eye, and detection of the resulting vibration using Doppler ultrasound. A dependence of the frequency of resonance of the eye on the IOP has been observed in both in vitro and in vivo experiments. Preliminary in vitro experiments have been performed using eviscerated and enucleated human and pig eyes. As little as 4 mm Hg change in IOP has been found detectable in these experiments. Preliminary in vivo experiments also showed promising results in this regard. We present a simple model for the resonances of the eye, a method to detect the amplitude of vibration using Doppler ultrasound and results from the in vitro and in vivo experiments.

Animals↗
PubMed1993

A study of macrophages, macrophage-related cells, and endothelial adhesion molecules in recurrent aphthous ulcers in HIV-positive patients.

The purpose of this immunohistochemical study was to investigate the presence and distribution of macrophages (CD11c+ and CD68+) and macrophage-related dendritic cells (factor XIIIa+ and CD36+) in early and late aphthous ulcers associated with HIV infection. To substantiate a mechanism by which these cells may move from the vascular compartment to tissue spaces, we also investigated expression of ELAM (endothelial leukocyte adhesion molecule), ICAM-1 (intercellular adhesion molecule), and CD18 (leukocyte function antigen). Numerous CD11c+ and CD68+ macrophages were seen in early lesions, though larger numbers of CD68+ cells were present in older lesions. No significant increases in factor XIIIa+ dendrocytes were seen in either early or late lesions, though dendrocytes appeared enlarged. CD36+ cells and CD18+ leukocytes were more numerous in early than in late aphthous ulcers. ELAM and ICAM expression was most intense on endothelial cells in early aphthous ulcers, with staining intensity fading toward the lesion periphery. Control specimens showed weaker ELAM and ICAM staining than did the ulcer specimens. Keratinocytes did not express ICAM. By virtue of their numbers, macrophages and macrophage subtypes appear to have a significant role in both the early and late stages of this disease. Although factor XIIIa-expressing dendrocytes may not have been more numerous in the ulcers, they appeared to be "activated" because of their prominence in the lesions and their occasional co-expression of CD68 antigen (KP1+). They may have a minor role in antigen processing, phagocytosis, and fibroplasia. ELAM and ICAM expression by endothelial cells provides a mechanism by which macrophages and other leukocytes can be recruited to the site of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1992

Immune-related disease and normal-tension glaucoma. A case-control study.

We reviewed the charts of 67 patients with the diagnosis of normal-tension glaucoma listed in the Bascom Palmer Eye Institute computer database. These patients were matched with respect to age, race, and sex with an equal number of patients having ocular hypertension. All medical diagnoses in the charts for both groups were tabulated and classified as either immune-related or non-immune-related. Twenty (30%) patients with normal-tension glaucoma had one or more immune-related disease(s) compared with five (8%) patients in the comparison group (P = .00134, McNemar statistic with continuity correction).

Aged↗
PubMed1990

Effect of human follicular fluids from pregnant and nonpregnant patients on the development of mouse zygotes in vitro.

Mouse zygotes were cultured in medium containing follicular fluid from patients who had follicles containing oocytes which fertilized, did not fertilize, or were atretic and who did or did not become pregnant after in vitro fertilization and embryo replacement. The inhibitory effect was least with the follicular fluid from follicles in which the oocytes subsequently fertilized, greater when the oocytes did not fertilize, and most inhibitory when the follicle contained an atretic oocyte. More mouse zygotes developed to blastocysts when culture medium was supplemented with follicular fluid from patients who became pregnant compared to those who did not become pregnant. There was no difference in pregnancy outcome when an oocyte which subsequently fertilized was obtained from the follicle. These results indicate that follicles contain a substance(s) which inhibits mouse zygote development in vitro and that the inhibitory activity is related to the developmental potential of the oocyte in the follicle.

Adolescent↗
PubMed1989

A three-year study of Salmonella dublin infection in a closed dairy herd.

Over a period of three years, Salmonella dublin was isolated occasionally from the faeces of nine adult cattle in a closed dairy herd. The organism was also isolated from 12 of the samples collected after parturition; isolations were made from newborn calves on 11 occasions, from a vaginal swab once and from a milk sample once. Nine of the isolations from the calves were made from swabs obtained within 24 hours of birth. Throughout the investigation isolations were made from heifers, steers and older calves and 11 infected animals were detected. S. dublin was widespread in the farm environment and it was concluded that environmental contamination was an important source of infection for animals of all ages, some of which may have become latent carriers. The family history of one cow, seven of whose offspring were infected with S dublin, suggested the possibility of vertical transmission. Without reliable tests to detect latent carriers, it is suggested that control of this infection must be based on improved hygiene and the use of vaccination to improve the immunity of the herd.

Animals↗
PubMed1988

A method for improved biometry of the anterior chamber with a Scheimpflug technique.

A new method is described for obtaining cross-sectional images of the anterior chamber. Photographs are obtained with a Scheimpflug slit-lamp camera. After cornea, iris, and lens surfaces are digitized, mathematical corrections are made for the camera distortion and for the refractive effects of the cornea. The reproducibility and accuracy of the method were tested and found to be adequate for clinical study of human eyes in physiologic or diseased states.

Analog-Digital Conversion↗
PubMed1982

The local and systemic IgA and IgG antibody responses of rabbits to a soluble inhaled antigen: measurement of responses in a model of acute hypersensitivity pneumonitis.

We evaluated local and systemic humoral responses to inhalational challenges with ovalbumin (OA) by measuring IgA and IgG isotypic antibodies to OA in serum and bronchoalveolar wash fluids (BAW), and by quantitating cells containing IgA, IgG, and anti-OA in lung, lymph nodes, spleen, and gut. Rabbit models of acute hypersensitivity pneumonitis and chronically-challenged "desensitized" animals were studied along with appropriate control animals. Systemic (via a toe pad) immunization or acute aerosol challenge with OA resulted in only trace amounts of IgG anti-OA antibodies in BAW and no apparent anti-OA-containing cells in the lung itself. Acute aerosol challenge of systemically immunized rabbits caused alveolitis, increased IgG anti-OA-containing cells in mediastinal and popliteal lymph nodes, and increased IgG anti-OA in BAW attributable to transudation from serum. Thrice-weekly inhalational challenge with aerosolized OA resulted in waning alveolitis, elevated concentrations of IgA and IgG anti-OA in BAW and serum, and increased concentrations of IgG and IgA anti-OA cells in the lung, but not in other tissues, including the gut. We conclude that these experiments have implicated IgG as well as IgA antibodies in local humoral responses to inhaled antigen, have not substantiated the notion of a common mucosal immune system involving lung and gut, have failed to demonstrate humoral tolerogenesis after inhalation of antigen, and have shown an effect of systemic priming on subsequent pulmonary immune responses in the models examined.

Alveolitis, Extrinsic Allergic↗
PubMed1981

Antigen-specific densensitization in a rabbit model of acute hypersensitivity pneumonitis.

Rabbits that had been prepared to develop acute alveolitis after aerosol challenge with simple protein antigens did not develop chronic alveolitis but rather gradually recovered despite continued challenge. Immunologic accompaniments of waning disease were compared in this model to those associated with intravenous injections of antigen causing "desensitization." We also studied the effects of aerosol challenge prior to systemic immunization, antigen specificity, and the duration of desensitization by aerosolized and intravenous antigen. We found that repeated aerosol or intravenous challenges produced antigen-specific desensitization in this model, and the effect lasted several weeks. Prior exposure to aerosolized antigen was not protective. Neither aerosol nor intravenous desensitization maneuvers abrogated antigen-specific lymphocyte blastogenesis, although an early transient fall did occur. Humoral responses were boosted. These findings suggest that chronic alveolitis is prevented in this model by specific desensitization, without the induction of true tolerance or of nonspecific anergy. Such immunoregulation may result from development of antigen-specific blockade or blocking factors (e.g., lymphokines), antigen-antibody complexes, or suppressor cells affecting specific effector cells. Evaluation of these mechanisms may have implications for diagnosis and prognosis in human hypersensitivity pneumonitis.

Acute Disease↗
PubMed1980

Systemic and local lymphocyte responses in experimental hypersensitivity pneumonitis.

The pathogenesis of hypersensitivity pneumonitis is incompletely understood; cell-mediated hypersensitivity mechanisms may be involved, but in vitro correlates have been studied in humans with inconclusive results. We used a rabbit model of hypersensitivity pneumonitis to study systemic and local antigen-specific lymphocyte responses as measured by in vitro incorporation of 3H-thymidine. Groups of animals were systemically immunized with ovalbumin and acutely or repeatedly challenged with aerosolized ovalbumin. Lymphocyte responses were measured in peripheral blood, mediastinal and popliteal lymph nodes, bronchus-associated lymphoid tissue, and bronchoalveolar wash fluids in these groups and in appropriate control animals. Lymphocyte proliferative responses to specific antigen, shown previously to be a T-cell response in this system, occurred after systemic or inhalation exposure to antigen. Acute alveolitis was associated with a decrease in peripheral blood lymphocyte responses and the presence of responsive lymphocytes in bronchoalveolar was fluids. Repeated inhalation challenge thrice weekly for 1 month, with waning of alveolitis, was not associated with significant changes in lymphocyte responsiveness. Antigen-specific lymphocyte blastogenesis did not define animals capable of developing alveolitis after aerosol challenge and did not appear, therefore, to distinguish effector cell activity in this model.

Alveolitis, Extrinsic Allergic↗
PubMed1979

Basophil chemotaxis under agarose: variability among guinea pig donors and response to sera of different species.

Guinea pig basophils were tested against chemotactic factor(s) generated from homologous and heterologous sera. An "under agarose" method of quantitating leukocyte chemotaxis was adapted to measure serum-derived basophil chemotactic factor(s) (BCF). The method was found to be simple, reproducible, and sparing of time and reagents and it provided simultaneous controls. Because of the economy of reagents compared with the Boyden chamber technique, basophils from individual guinea pigs could be studied and were found to be variable in responsiveness. A definite difference in the response of guinea pig basophils to zymosan-activated sera of various other species was demonstrated. Guinea pig basophils responded to zymosan-activated serum from guinea pig and rat but failed to respond to zymosan-activated serum from human, hamster, rabbit, or cow. Optimal conditions were determined for cell numbers, serum activation and dilution, and migration times for studies of guinea pig BCF. The under agarose technique provides a practical alternative to chamber methods for the study of basophil chemotaxis. Although guinea pig basophils do not respond to human serum-derived BCF, the economy of reagents with this technique gives promise toward adaptation of the method to studies of human basophil chemotaxis.

Animals↗
PubMed1979

Strychnine intoxication.

Strychnine intoxication is manifested by agitation, muscle spasms, and convulsions. We report a case in which intractable convulsions led to severe lactic acidosis which secondarily resulted in visceral (lung, heart, kidney, liver, and brain) collapse and death. Aggressive therapy instituted in the emergency department and aimed at control of seizure activity and lactic acidosis may be lifesaving.

Acidosis↗
PubMed1978

Chronic experimental interstitial pneumonitis in the rabbit.

The effects on the lungs of chronic aerosol and intravenous antigen challenges in preimmunized and control rabbits were studied. Soluble and particulate antigens included ovalbumin, keyhole limpet hemocyanin, antigen-adsorbed latex particles, glutaraldehyde cross-linked ovalbumin, and killed bacille Calmette-Guérin (BCG). Despite the development of acute alveolitis in sensitized animals, chronic aerosol challenge with both soluble and particulate antigens failed to produce chronic interstitial lung disease. Chronic intravenous challenge with killed BCG, but not other particulate antigens, resulted in a progressive interstitial pneumonitis, with evidence of fibrogenesis in animals that had been presensitized to tuberculin by toepad injection of complete Freund's adjuvant. Adaptive alveolar clearance mechanisms thus appear to protect rabbits from chronically inhaled antigen. Pulmonary circulatory clearance of BCG, however, results in an interstitial pneumonitis that is dependent on previous sensitization.

Aerosols↗