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Biomedical subjects

T John

Publications and source records attributed to T John.

At least 55 records · Page 3Linked to original sources

Adherence of Acanthamoeba castellanii cysts and trophozoites to unworn soft contact lenses.

Contact lens-related Acanthamoeba keratitis has been associated with the use of soft contact lenses and homemade saline solutions. We studied the adherence of Acanthamoeba to unworn extended-wear soft contact lenses on a human corneal isolate of Acanthamoeba castellanii suspended in normal saline (cysts, 6.3 x 10(5)/ml; trophozoites, 3.6 x 10(5)/ml). Unworn hydrogel contact lenses (polymacon, water content 38.6%; 50 lenses, 400 lens segments) were exposed to A. castellanii cysts or trophozoites with or without stirring. After exposure for zero to seven hours, soft contact lenses were or were not washed, and the A. castellanii adherence was determined with a standardized light-microscopy technique (40 fields, ten lens segments for each count) and with scanning electron microscopy. Both cysts and trophozoites adhered to the unworn soft contact lenses. Trophozoites showed acanthopodia, lobopodia, and filopodia. This study indicates that both A. castellanii cysts and trophozoites can firmly adhere to unworn soft contact lens. Such adherence may play a role in the pathogenesis of soft contact lens-related Acanthamoeba keratitis.

Acanthamoeba↗

Adherence of viable and nonviable bacteria to soft contact lenses.

Bacterial viability in bacterial adherence to new soft contact lenses (SCLs) was studied by exposing polymacon and lidofilcon A lenses to Pseudomonas aeruginosa: L, live, untreated bacteria; H, bacteria heated for 1 h at 100 degrees C; and P, bacteria treated with 3% hydrogen peroxide for 1 h. Cultures of groups L, H, and P showed heavy, no, and minimal bacterial growth, respectively. Scanning electron microscopy (SEM) showed significantly less bacteria on new SCLs in groups H and P. Transmission electron microscopy (TEM) showed that bacterial shape was mostly preserved in all groups, with marked intracellular and cell membrane changes and breaks (groups H and P), margination of intracellular electron-dense material (group H), and central and peripheral vacuolation (group P). Adherence to new SCLs appears to be an active process, as killed or altered bacteria adhere less.

Bacterial Adhesion↗

Epithelial abnormalities and sterile ulceration of epikeratoplasty grafts.

Six epikeratoplasty (EKP) specimens were obtained 1 to 10 months after refractive keratoplasty for aphakia (2 cases), keratoconus (1 case), and myopia (3 cases). The EKP grafts were removed because of postoperative complications such as delayed reepithelialization, lenticule edema, stromal ulceration, graft opacification, and inability to improve vision in a clear graft. The extent of epithelial abnormalities was associated directly with the severity of structural changes in the underlying basal lamina, Bowman's layer, and stroma as evidenced by electron microscopic examination. Epithelial defects were associated with varying degrees of sterile stromal ulceration of the underlying lenticule. In one case, an extensive full-thickness ulceration of the EKP button occurred in the area of persistent epithelial defects and was associated with a major ulceration of the underlying recipient's corneal stroma. Removing the failing button halted the ulcerative process with prompt reepithelialization. In the absence of inflammation and infection, the persistent epithelial abnormalities and defects leading to proteolytic degradation of the EKP buttons constitute an important mechanism of graft failure with major visual consequences and possibly irreversible ocular damage.

Adult↗

Retinal pigment epitheliopathy and neuroretinal degeneration in ascarid-infected eyes.

The generalized choroidal and retinal response to a focal nonreplicating infection of the eye with ascarid larvae was examined in an animal model. Intravitreal injection of Ascaris suum larvae in guinea pigs induced a diffuse eosinophilic choroiditis, retinal pigment epitheliopathy and neuroretinal degeneration, distant from focal reactions about larvae. As the choroiditis progressed, inflammatory cells separated the choriocapillaris from Bruch's membrane, and the endothelial cells lost their fenestrations. Focal disruption of the elastic and outer collagenous layers of Bruch's membrane occurred, but inflammatory cells rarely invaded the retina. Progressive generalized degenerative and proliferative RPE changes produced a multilayered RPE with loss of cell polarity, RPE basal infoldings and apical microvilli, formation of multiple giant cystic spaces, and proliferation of subretinal fibroblasts. Early loss of photoreceptor outer segments progressed to a generalized disruption of the outer neural retina and cystoid retinal degeneration. Eosinophil mediators and alterations of the choriocapillaris may contribute to the generalized progressive retinal degeneration distant from a parasite larva in ascarid-infected eyes.

Animals↗

Outpatient keratoplasty.

Outpatient keratoplasty in 103 patients (46 males and 57 females ranging in age from 1 to 90 years) produced no instances of infection, shallow or flat anterior chambers, or anterior synechia formation. Postoperative discomfort was minimal.

Adolescent↗

Recovery of corneal sensitivity in grafts following penetrating keratoplasty.

Corneal sensitivity was tested in 145 cases of clear corneal transplants using Cochet-Bonnet aesthesiometer. The central area of corneal transplants was found to be either completely anesthetic or markedly hypesthetic even 32 years following corneal transplantation, as exemplified in a patient who had surgery for keratoconus. Age, preoperative diagnosis, contact lens wear, diabetes, or length of postoperative period had no correlation with sensitivity in corneal grafts. In cases with a preoperative diagnosis of failed graft, even the peripheral recipient cornea was found to be relatively hypesthetic. The observations from this study that the central area of corneal graft never recovers normal sensitivity may have significant implications on the epithelial cell integrity of corneal grafts.

Adult↗

Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin.

Repeated topical applications of fluoresceinyl ovalbumin (FL-OA) to the conjunctival sac of guinea pigs sensitized them for conjunctival type 1 hypersensitivity reactions and mast cell degranulation. Guinea pigs infected with Ascaris suum, with high titers of circulating anti-A suum IgE and IgG1 antibody, also produced conjunctival type 1 reactions on topical challenge with A suum antigen. These reactions were no more intense than those of animals topically sensitized and challenged with FL-OA, which in some instances had no detectable serum homocytotropic antibody. Persistently reactive animals that had undergone repeated type 1 conjunctival reactions had histological findings (eg, papillary changes with extensive epithelial eosinophil infiltrates, epithelial thickening or thinning, numerous goblet cells, subepithelial lymphoid cell infiltrates, and new vessel formation) resembling those of human atopic vernal conjunctivitis.

Animals↗

Electron microscopic study of corneal epithelial-endothelial interactions in organ culture.

The interactions between rabbit corneal epithelium and endothelium were investigated in an organ culture model using scanning electron microscopy and correlative light microscopy. Following mechanical removal of corneal endothelium, corneal epithelium was observed to migrate across the cut surface of the corneal stroma and onto the denuded Descemet's membrane after 48 hours in organ culture. By 72 hours, a distinct line of contact between the migrated epithelium and endothelium was established. Following epithelial-endothelial contact, no cellular migration occurred. Corneal endothelial inhibition of epithelial migration may be a major factor in the prevention of surface epithelial invasion and proliferation following surgery and trauma.

Animals↗

The myofibroblastic component of rubeosis iridis.

Nineteen blind eyes enucleated for painful angle closure-glaucoma secondary to iris neovascularization (rubeosis iridis) were examined by scanning electron microscopy and correlative light and transmission electron microscopy. Fresh and deparaffinized tissue from patients with diabetes mellitus, central retinal vein occlusion, and retinoblastoma were studied. Scanning electron microscopy revealed extensive peripheral anterior synechia formation and flattening and effacement of the anterior iridic surface by a confluent fibrovascular membrane. New vessels on the anterior iris uniformly were hidden beneath a clinically inapparent, superficial layer of myofibroblasts, ie, fibroblastic cells with smooth muscle differentiation. Myofibroblasts may provide the motive force for synechial closure and ectropion iridis in neovascular glaucoma.

Fibroblasts↗

In vitro interaction of eosinophils from ascarid-infected eyes with Ascaris suum and Toxocara canis larvae.

The role of eosinophils in ocular ascarid infection is studied in an animal model. Primary intravitreal infection of guinea-pig eyes with ascarid (Toxocara canis, Ascaris suum) second-stage (L2) larvae resulted in an anterior chamber exudate containing 98% or more eosinophils. Anterior chamber aspirates were cultured in RPMI media 1640 with T. canis or A. suum L2 larvae at 37 degrees C for 1-96 hours. The in vitro interaction of eosinophils with L2 larvae was studied by light, and scanning and transmission electron microscopy. Eosinophil interaction with L2 larvae in vitro was dependent upon soluble factors present in the anterior chamber aspirates from the infected eyes. Eosinophils adhered firmly to the surface of the L2 larvae, to a larval sheath, or to attached eosinophils. Eosinophils interacting with larvae displayed a range of granular matrix changes, core duplication, and reversal of the relative electron densities of the core and matrix, suggestive of eosinophil activation. An eosinophil secretory granule was seen to empty its contents onto a T. canis L2 larval surface. Electron-dense material was observed in the interphase between eosinophils and the larval cuticle or sheath. Large lipid droplets within muscle cells and ballooned-out epidermal cells were seen within larvae immediately beneath adherent eosinophils. Parasites were able to partially evade interaction with eosinophils in culture by shedding their sheaths. A similar phenomenon in vivo may allow the parasite to migrate from a site of inflammation. It is possible that a discarded sheath or membrane serves as an antigenic stimulus for a local intraocular granulomatous reaction free of parasite.

Animals↗

Adjuvant immunotherapy (BCG) in stage D prostate cancer.

Thirty-three patients with advanced prostate cancer were prospectively randomized to receive either Bacillus Calmette-Guerin (BCG) adjuvant immunotherapy plus conventional therapy or conventional therapy alone. Conventional therapy consisted of estrogens or observation. There was a statistically significantly (p less than 0.05) longer survival in the 16 BCG-treated patients (42 weeks) than in the 17 control patients (29 weeks).

Adenocarcinoma↗

Adjuvant immunotherapy with bacillus Calmette-Guérin in prostatic cancer.

Ninety-two patients with histologically proved prostatic cancer were studied. Forty-six patients were treated with bacillus Calmette-Guérin (BCG) adjuvant immunotherapy, and 46 other patients, matched for stage and hormone therapy, served as controls. Survival from the time of histologic diagnosis was sixteen and one-half months longer (thirty-seven and one-half versus twenty-one months) in the BCG-treated patients. There was no mortality and only minimal morbidity. Changes in some immunologic parameters (white blood cell count, skin tests) suggest an immune response.

Aged↗

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients.

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients' leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of "stimulation" of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Adenocarcinoma↗

Prostate carcinoma: immunostaging and adjuvant immunotherapy with BCG.

Thirty-three patients with histologic diagnosis of adenocarcinoma of the prostate were entered into separate protocols: 1) immunostaging, and 2) BCG adjuvant immunotherapy. Immunostaging is a new method of assessing patients immunologically prior to and after immunotherapy. Thirty of these patients were immunostaged with the use of humoral and cellular immune parameters. A positive correlation was noted between the patient's immunostage and the clinical stage of his cancer. The 33 patients with a histologic diagnosis of adenocarcinoma of the prostate were entered into an ongoing protocol of adjuvant BCG immunotherapy in addition to conventional therapy (19 patients received BCG and 14 served as controls). The patients receiving BCG had a longer mean survival time; minimal morbidity and no mortality resulted from this therapy.

Adenocarcinoma↗

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. III. Inhibition of leucocyte migration.

Host cellular responsiveness to tumour was evaluted in 37 patients with varying degrees of clinically active and inactive adenocarcinoma of the prostate by direct inhibition of leucocyte migration (ILM) employing saline extracts of pooled allogeneic normal, benign and malignant prostatic tissue as a source of antigen. The majority of these patients had received or were receiving conventional therapy at the time of evaluation. 13 (35%) prostatic cancer patients possessed clinically significant specific reactivity to malignant prostatic tissue, whereas only 1 (8%), of 13 control patients (11 healthy adults and 2 patients with carcinoma other than of the prostate: bladder and penis) possessed comparable reactivity. While the wide range of specific reactivity observed overall, including 'stimulation' of migration, compared with the mean percent ILM was very large, the SD of the mean specific percent ILM in the 13 prostatic cancer patients possessing clinically significant specific reactivity to malignant prostatic tissue, was most respectable. Since all reactions were allogeneic, these results indicated that prostatic cancer patients possessed cell-mediated immunity to presumably common prostatic tumour-associated antigens. Further evaluation disclosed that the incidence of patients possessing clinically significant reactivity to malignant tissue was almost identical regardless of the patient's stage of malignancy, histological grade of tumour, or clinical status. The degree of sensitization of clinically significant reactivity to malignant tissue was, however, greater in patients with localized disease, low grade tumour, and clinically inactive disease, than in patients with advanced disease, high-grade tumour, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of subsequent clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43%) of 7 patients available for routine follow-up. Correlation in four patients was questionable due to the observations of 'stimulation' of migration rather than inhibition. While providing initial preliminary evidence of the presence of cell-mediated anti-tumour immunity in patients with prostatic cancer and promise of a possible prognostic index, the wide range in the variability of cellular responsiveness and the failure to identify clinically significant reactivity to malignant prostatic tissue in the majority (65%) of the patients evaluated, raises concern as to whether ILM employing saline extracts will provide the necessary in vitro assay of cellular responsivenss for the evaluation of prostatic cancer patients.

Adenocarcinoma↗