Biomedical subjects

A Heiligenhaus

Publications and source records attributed to A Heiligenhaus.

At least 55 records · Page 3Linked to original sources

PubMed1996

T-cell subsets and T-cell receptor V beta utilization by Igh-1-congenic mice in herpetic retinal necrosis.

BACKGROUND: After unilateral anterior chamber (AC) inoculation with herpes simplex virus type 1 (HSV-1), C.B-17 and BALB/c congenic mice, which differ only in a limited region around the lgh-1 locus on chromosome 12, show a striking difference in susceptibility to development of encephalitis and contralateral necrotizing chorioretinitis. METHODS: After AC inoculation with HSV-1 (KOS), C.B-17 and BALB/c mice were followed up for the clinical signs of encephalitis and chorioretinitis. At different time points following inoculation, lymphocytes isolated from the spleen were triple-stained with antibodies directed against CD4 or CD8, IL-2R, and various V beta T-cell receptor (TCR) subsets, and were analyzed by flow cytometry. RESULTS: These lgh-1-disparate congenic mice showed differences in the time course of splenic V beta T-cell receptor (TCR) usage in both CD4+, IL-2R+ and CD8+, IL-2R+ T cells. By day 1 post infection (p.i.), C.B-17 mice showed an increase of V beta 8 and V beta 9 TCR by both CD4+, IL-2R+ and CD8+, IL-2R+ splenic T cells. Susceptible BALB/c mice delayed the increase of splenic V beta 8 and V beta 9 TCR by CD4+, IL-2R+ T cells, which was noted by day 4 p.i. Furthermore, in BALB/c mice the usage of V beta 9 by CD8+ cells was increased by day 6 p.i. CONCLUSIONS: Our findings indicate that early preferential splenic usage of a restricted repertoire of TCR occurs after ocular inoculation with HSV-1 in resistant C.B-17 mice. Such preferential TCR usage by activated T cells may prevent viral replication in the brain and contralateral eye and may be linked to protection from development of encephalitis and destructive herpesmediated ocular inflammation.

Animals↗

PubMed1996

Histology and immunopathology of systemic lupus erythematosus affecting the conjunctiva.

Systemic lupus erythematosus (SLE) is an autoimmune disease occasionally involving the conjunctiva, sclera or cornea. The immunopathology of the active epibulbar lesions has not been studied in detail. Conjunctival biopsies from 11 SLE patients with active epibulbar lesions and from 12 age-matched individuals undergoing cataract surgery were analysed by light microscopy, immunofluorescence and immunoperoxidase techniques. SLE patients presented with scleritis (3 cases), peripheral ulcerative keratitis (5 cases) or progressive cicatrising conjunctivitis (5 cases). Histologically, SLE specimens showed moderate subepithelial and perivascular mononuclear cell infiltration or granuloma formation in the substantia propria, and squamous metaplasia; thrombosis was not seen. Immunoreactant deposition was present at the epithelial basement membrane in 4 of 5 cases with cicatrising conjunctivitis. Vascular immunodeposits wer detected in 4 cases. The epithelium showed increased T helper cells (CD4+), granulocytes and natural killer cells (CD67+), dendritic cells (CD1+), and an increase in HLA-DR expression compared with normal tissue. In the substantia propria, B cells (CD22+), macrophages (CD14+), dendritic cells, activated T cells (CD25+, CD3+), the T helper (CD4+)/T suppressor (CD8+) ratio and HLA-DR expression were all increased. These observations suggest that the rare epibulbar manifestations in SLE result from immune-complex-mediated reactions.

Adolescent↗

PubMed1996

Long-term results of pars plana vitrectomy in the management of intermediate uveitis.

Pars plana vitrectomy is a useful tool for the management of certain complications in chronic intermediate uveitis. Media opacities obscuring the visual axis, vitreous membranes causing tractional retinal detachment, macular puckers, and ciliary traction leading to hypotony are clear indications for this approach. Furthermore, it has been suggested that vitrectomy may have a favorable long-term effect on the course of disease. The procedure may achieve regression of inflammation, tapering of immunosuppression, and improvement of cystoid macular edema. However, randomized prospective trials are still needed to define the role of vitrectomy in altering the course of uveitis.

Chronic Disease↗

PubMed1996

[Treatment with tissue plasminogen activator (tPA) in risk patients with fibrin reactions after cataract operations].

The postoperative course after cataract surgery can be complicated by the formation of severe fibrinous membranes, especially in cases with previous goniotrepanation, after syn echiolysis, iridotomy or iris suturing, and in patients with diabetes or uveitis. This study retrospectively analyzes the efficacy of intraocular tissue plasminogen activator (tPA) for fibrinolysis in these conditions commonly considered as contraindications to tPA therapy. When antiinflammatory therapy was unsuccessful in lysing fibrinous membranes, 10 micrograms of tPA (Actilyse) was injected into the anterior chamber following the first postoperative day (n = 15). In addition, topical corticosteroids and cycloplegics were given postoperatively. Lysis of the fibrinous membranes was achieved in all patients. However, in three cases lysis was incomplete or recurred. Complications of intraocular tPA therapy consisted of mild hyphema (n = 1) and transient dysfunction of the corneal endothelial cells (n = 2). In conclusion, the results suggest intraocular low-dose tPA as an effective approach for the treatment of severe fibrinous membranes after cataract surgery even in high-risk patients.

Adolescent↗

PubMed1995

Immunisation against HSV-1 keratitis with a synthetic gD peptide.

The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were immunised subcutaneously with a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system. Low dosages (31 micrograms) of gD(5-23) protected against encephalitis and HSK. Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant. Latent infection was found in all control mice but in only 50-75% of immunised mice. The most potent protection was correlated with anti-HSV-1 neutralising antibodies of IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1 antibodies. Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis.

Amino Acid Sequence↗

PubMed1995

[Pterygium excision with intra-operative administration of low dosage mitomycin C].

Pterygium excision with postoperative instillation of mitoymcin C (MMC, 0.4 mg/ml) is encouraging because of the technical simplicity and low recurrence rates, but serious postoperative complications have been described (scleral necrosis, corneal perforation, glaucoma, cataract). The authors studied the efficacy and safety of pterygium excisions with a single intraoperative application of low-dose MMC (0.2 mg/ml). Pterygium excision (bare sclera technique) was performed in 18 patients with primary or recurrent pterygia. MMC (0.2 mg/ml) was applied intraoperatively (5 min) to the exposed sclera. Patients were followed up for signs of recurrence and complications. There were four recurrences (mean follow-up 13.8 months). Postoperative complications consisted of granuloma formation (n = 2). Delayed conjunctival healing was observed in all cases. Scleral necrosis, corneal complications, cataract, or glaucoma were not seen. Intraoperative application of MMC apparently reduces the recurrence rate after pterygium excision. The use of a 0.2 mg/ml concentration of MMC appears to be safe.

Adult↗

PubMed1995

[Glycoprotein D (5-23) specific Th2-T-cell line induces HSV-1 keratitis].

BALB/c inbred Igh-1-disparate mice exhibit different susceptibility to the development of HSV-1 stromal keratitis (HSK), which may be due to the differential immune regulation. CD4+ T lymphocytes may be critical for the disease induction. A T-cell line (CD4+, T-cell receptor V beta 8+, interleukin-4+) specific for the N-terminal amino acids 5-23 of glycoprotein D from HSV-1 [gD(5-23)] was established from HSK susceptible C.AL-20 mice. HSK-resistant C.B-17 mice, and HSK-susceptible BALB/c mice were injected intraperitoneally with cells (5 x 10(5)/mouse) alone or combined with HSV-1 corneal inoculation (10(5) PFU, KOS strain). Control groups were injected with HSV-antigen-unrelated cells (PPD specific), or were only HSV-1 infected. Migration of the adoptively transferred gD(5-23) Th2 cells was analyzed by histology, by immunohistochemistry and by cell membrane labelling (PKH26). The transfer of gD(5-23) cells accelerated the disease onset (day 2, compared to day 7 without cells). The transfer of gD(5-23) cells increased the incidence of HSK (BALB/c 100%, C.B-17 20%) compared to mice that were only infected with HSV-1 (BALB/c 75%, C.B-17 0%). Keratitis was more severe in mice injected with gD(5-23) cells. In contrast, the transfer of PPD-specific cells did not influence the disease patterns. Mice injected with gD(5-23) cells and not inoculated with HSV-1 did not develop keratitis. The results suggest that CD4+ MHC class II, V beta 8+, IL-4 expressing T-cells (T helper 2) may be important for the induction of HSK.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

[Diagnosis and and differentiation of dry eye disorders].

Artificial tears often fail in dry eye patients. Our goal was to establish a diagnostic approach that involves alternatives that are more effective for the treatment. We examined 110 patients with dry eyes not stabilized by artificial tears: medical history, visual acuity, slit lamp examination, rose bengal stains and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression cytology, and lid transillumination. This allowed disturbances of the three layers of the tear film (lipid, aqueous, mucin) to be differentiated. Cellular damage of the ocular surface was evaluated and scored by slit lamp examination, rose bengal staining, and impression cytology. Only 8% of the patients with "sicca syndrome" had exclusive aqueous deficiencies amenable to artificial tears. In contrast, lipid deficiencies (chronic blepharitis) were determined most frequently (78%). Twenty-six percent had disturbances in two or more layers of the tear film. The diagnostic strategy of differentiating disturbances of the layers of the tear film offers a more specific approach to the treatment of dry eyes.

Adult↗

PubMed1994

Histological and immunopathological analysis of T-cells mediating murine HSV-1 keratitis.

BACKGROUND: Thymus-derived lymphocytes play a critical role in the development of herpes simplex keratitis (HSK). T-cell subsets defined by their expression of various T-cell receptor (TCR) V beta segments were studied following corneal HSV-1 infection (p.i.). METHODS: Conjunctiva, corneal limbus and corneal stroma of two inbred BALB/c congenic mouse strains which differ only in the gene products closely linked to the Igh-1 locus on chromosome 12 were analyzed. RESULTS: While C.B-17 mice (Igh-1b) were resistant to HSK, C.AL-20 mice (Igh-1d) clinically developed severe necrotizing keratitis by day 11 p.i. The corneal stroma of C.B-17 mice remained clear, while it was increasingly infiltrated by mononuclear cells and neutrophils in C.AL-20 mice by day 11 p.i. In C.B-17 mice, Thy1.2+ cells were found in the conjunctiva between days 2 to 4 p.i., and subsequently decreased. Only a few Thy1.2+ cells were found in the limbus, and no such cells were found in the stroma. In contrast, in C.AL-20 mice the numbers of Thy1.2+ cells (activated CD4+, V beta 8+ T cells) profoundly increased in the conjunctiva by day 4 p.i. These cells infiltrated the limbus between days 7 and 11 p.i. and eventually entered the stromal tissue by day 11 p.i. CONCLUSIONS: Our data suggest that the HSV-1-induced corneal tissue destruction is mediated by mononuclear cells and neutrophils and that these cells are probably attracted into the cornea by cytokines elaborated by activated CD4+, V beta 8+ T cells.

Animals↗

PubMed1994

[Therapy of dry eye disorders].

BACKGROUND: The treatment of dry eyes with artificial tears often fails. We differentiated the disturbances of the three layers of the tear film in 90 such patients. This showed that only 11.1% had aqueous deficiency, while 42.3% had combined disturbances of different layers of the tear film, and 76.7% had lipid deficiencies. PATIENTS AND METHODS: We now studied the efficacy of a therapeutic approach, which intended to stabilize each individual deficiency of the three layers of the tear film (follow-up > or = 6 months). The medical history, visual acuity, slit lamp examination, rose bengal stains and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression cytology, and lid transillumination were analyzed. RESULTS: Therapy was beneficial in all patients (n = 90) with regard to the symptoms and the objective parameters. Artificial tears applied strictly were without preservatives. Patients with toxic conjunctivitis induced by high dosages of eye drops were often stabilized through withdrawing the medication. The frequency of applying artificial tears was significantly tapered by punctum plugs and -coagulation. Tarsorrhapies were helpful in the most severe cases. Topical retinoids significantly reduced the symptoms and increased the goblet cell density. Treating chronic blepharitis was very sufficient, when initiated by topical steroids and Tetracycline, and systemical Doxycycline. CONCLUSIONS: Differentiating the disturbances of the three tear film layers in "sicca syndrome", and stabilizing each component is more effective than artificial tears alone.

Combined Modality Therapy↗

PubMed1994

[Ocular involvement in Whipple disease].

PATIENTS AND METHODS We present a 57-year-old white man with progressive deterioration of vision, who had a prolonged history of weakness, migratory arthralgias and loss of weight. Bilateral panuveitis, with iritis, inflammatory vitreous opacities associated with small, round, grayish retinal lesions. The duodenum showed a swollen mucosa, which was flecked over with pinpoint grayish grains. A small-bowel biopsy disclosed PAS-positive granules in the macrophages of the lamina propria mucosa, pathognomonic of Whipple's disease. RESULTS After antibiotic treatment with trimethoprim and sulfamethoxazole there was no relapse of the panuveitis during the follow-up period of 18 months.

Humans↗

PubMed1994

Long-term results of pars plana vitrectomy in the management of complicated uveitis.

This retrospective study evaluates the long term efficacy of pars plana vitrectomy on the preservation of vision in complicated chronic uveitis, including endogenous intermediate uveitis and other entities. Combined vitrectomy-lensectomy was performed in 10 eyes with complicated cataracts, and 18 vitrectomies were done without lensectomies. The mean follow up was 45 months. Additional retinal surgery (for example, scleral buckling) was performed in five eyes. Visual acuity improved in 23 eyes (82.8%) following surgery, with 16 eyes (57%) achieving a vision better than 6/24. The main causes for vision less than 6/24 were persistent cystoid macular oedema (three eyes), macular puckers (one eye), retinal vascular obliterations (four eyes), optic atrophy (five eyes), and chorioretinal scars (seven eyes). Postoperative complications were cataract formation (seven eyes), cystoid macular oedema (one eye), and tractional retinal detachments (three eyes). The surgical intervention resulted in a remarkable reduction of the severity of inflammation or frequency of exacerbations, and allowed significant tapering (11 eyes) or withdrawal (11 eyes) of the topical steroids, or oral corticosteroids (10 cases). Pre-existent cystoid macular oedema resolved in three eyes. Pars plana vitrectomy, eventually combined with lensectomy, may visually rehabilitate eyes with chronic uveitis and media opacities, and may reduce the activity of disease postoperatively.

Adolescent↗

PubMed1994

CD4+V beta 8+ T cells mediate herpes stromal keratitis.

T lymphocytes are critical in mediating herpes simplex stromal keratitis (HSK). Using immunohistologic methods, we studied the T cell subsets and the T cell receptor variable region (TCR V beta) repertoire of T cells in the eye after corneal infection with HSV (KOS strain). We investigated the possibility that there might be differential V beta preferential usage in HSK resistant and susceptible BALB/c congenic mice that differ only in a small region associated with the Igh-1 gene locus. The inflamed corneas of HSK susceptible C.AL-20 mice were mainly infiltrated by CD4+ cells and by V beta 8 expressing cells. Such T cells were not seen in the corneas of resistant C.B-17 mice. Our results indicate that CD4+V beta 8+ cells are involved in mediating HSV-1 stromal keratitis.

Animals↗

PubMed1994

[Argon laser trabeculoplasty in chronic simple glaucoma with visual field defects and papillary damage].

It has been recently demonstrated that the intraocular pressure (IOP) after argon laser trabeculoplasty (ALT) in primary open-angle glaucoma rises in the long term. The present study analysed the effect of the postoperative rise in IOP in 36 patients (group A) with glaucomatous optic nerve damage or visual field defects. The results were compared with those in 37 patients without such glaucomatous damage (group B). The IOP, the cup-disk ratios and the visual fields (Goldmann) were retrospectively studied. All patients were under topical glaucoma medication. At the end of the follow-up (group A 20.2 +/- 3.39 months, group B 17.4 +/- 3.59 months), the IOP was uncontrolled in both study groups, and visual fields and disc cupping had worsened in both groups. The results indicate that ALT should not be considered in patients with optic disc damage or glaucomatous visual field defects.

Aged↗

PubMed1994

[T-cell-induced prevention of HSV-1 keratitis by immunization with the synthetic peptide of glycoprotein D].

C.AL-20 mice susceptible to herpes simplex virus (HSV) were protected against HSV keratitis (HSK) and encephalitis by subcutaneous immunization with synthetic peptide corresponding to the N-terminal amino acid residues 5-23 of HSV glycoprotein D, which is a dominant immunogen of HSV-1. Protection against HSV was related to a potent humoral anti-HSV response. FACScan analysis revealed that CD4+V beta 8(1.2)+ cells in the spleen were markedly decreased 2 days after HSV challenge, and CD8+ cells were increased. Numerous CD4+ and V beta 8(1.2)+ cells were found in the corneal tissue from HSV-infected sham-immunized mice; no such cells were seen in gD(5-23) immunized mice. No cytotoxic cells were detected in the corneas or spleens of gD(5-23) immunized mice, and these mice had decreased DTH responses. Protection against HSV through immunization with gD(5-23) involves humoral and cellular immune mechanisms. CD4+V beta 8(1.2)+ maybe critical in mediating the pathology of HSK. CD8+ cells may be protective by non-cytotoxic mechanisms. Our results suggest that gD peptides may be potent as vaccines against HSV.

Animals↗

PubMed1994

The role of macrophages in the pathogenesis of HSV-1 induced chorioretinitis in BALB/c mice.

PURPOSE: To examine the effects of modification of immune effector cells, including macrophages, in the pathogenesis of herpes simplex virus retinitis in BALB/c mice. METHODS: Two intravitreal injections (2 microliters each) of anti-CD11b monoclonal antibody (mAb) [13 micrograms/microliters] were administered to the contralateral eyes of 10 BALB/c mice on days 6 and 8 after HSV inoculation into the right anterior chamber (AC) with HSV-1. A control group consisted of mice injected with anti-HLA-DR mAb in the same fashion. Specific macrophage depletion was performed in an additional group of 12 BALB/c mice by intravenous (i.v.) injection of dichloromethylene diphosphonate (Cl2MDP)-liposomes 7 days before AC HSV-1 inoculation into the eye. Control group consisted of mice receiving i.v. PBS-liposomes. Mice were clinically observed for 14 days postinfection, and the incidence of chorioretinal disease was confirmed by histopathologic studies. RESULTS: Intravitreal injections of anti-CD11b mAb produced a dramatic suppression of the contralateral retinal necrosis (2 of 10 mice) compared to 9 of 10 controls receiving an irrelevant antibody therapy (P < 0.05). Mice treated with i.v. Cl2MDP-liposomes also showed a significant inhibition of the development of contralateral chorioretinitis, with only 3 of 12 mice developing retinal disease compared to 9 of 12 mice from the control group (P < 0.05). FACS analysis performed on peripheral blood and spleen cells showed a significant depletion of Mac-1+ cells of Cl2MDP-liposome-treated but not of PBS-liposome-treated mice (controls). CONCLUSION: Intravitreal anti-CD11b mAb therapy, a broadly directed depletion strategy against many effector cells (macrophages, granulocytes, natural killer cells, and even cytotoxic T-cells) was most efficient in suppressing the HSV-1 induced contralateral disease. A more specific technique (i.v. Cl2MDP-liposome therapy) to deplete macrophages also produced a significant inhibition of HSV-1 induced contralateral chorioretinitis. These findings suggest that macrophages are important participants in the effector phase of the destructive inflammatory immune response induced by HSV-1 in the eye.

Animals↗

PubMed1993

Exacerbation of murine herpes simplex virus-mediated stromal keratitis by Th2 type T cells.

Corneal infection of susceptible mice with HSV-1 causes herpetic stromal keratitis (HSK), which serves as a model of human HSK. To study the properties of the T lymphocytes involved in HSK, susceptible mice were immunized with the synthetic peptide corresponding to the amino terminal of HSV-1-associated glycoprotein D (gD 5-23). A CD4+ long-term T cell line and a clone bearing V beta 8.2 TCR were derived from peptide-primed lymph node cells. These T cells recognize gD 5-23 peptide in the context of I-Ed and require CD4 and LFA-1 for Ag-specific proliferation. Significantly, a truncated peptide gD 15-23 induced vigorous proliferation, indicating that these 9 amino acids constitute an epitope recognized by these T cells. The gD-specific T cells produced IL-4 and used it as the autocrine growth factor and hence belong to the Th2 subtype. Adoptive transfer of gD-specific Th2 cells into susceptible mice increased both the onset and severity of HSK after corneal HSV-1 infection. Injection of gD-specific Th2 cells without HSV-1 infection failed to cause eye damage. In addition, an irrelevant Ag-specific Th2 clone failed to induce similar tissue damage when the corresponding Ag was applied to the eye. These data indicate that the T cell-mediated exacerbation of HSK in these studies is dependent on the specific recognition of gD after corneal HSV-1 infection. Finally, gD-specific Th2 cell transfer also rendered HSK-resistant mice susceptible for HSK, suggesting that the freedom from HSK in resistant mice may primarily be due to their inability to produce the pathogenic Th2 cells. The data collectively implicate an important role for Th2 cells in the induction of HSV-mediated keratitis in mice.

Amino Acid Sequence↗

PubMed1993

Long-term results of mucous membrane grafting in ocular cicatricial pemphigoid. Implications for patient selection and surgical considerations.

BACKGROUND: Buccal mucous membrane grafting was performed in 26 eyes of 20 patients with advanced ocular cicatricial pemphigoid. The disease causes abnormalities of the eyelid margin and conjunctiva, which results in mechanical damage to the cornea. The authors' short-term results showed that mucous membrane grafting was effective in reversing these abnormalities if the disease was first medically controlled by chemotherapy or was in remission. METHODS: At the end of 2 years of follow-up, the authors reviewed all records and photographs of these patients. RESULTS: Serious postoperative corneal complications developed in 16 eyes (61.5%), causing worsened visual acuity in 8. The postoperative complications were associated with severe keratoconjunctivitis sicca in 14 eyes (87.5%), progression of subepithelial conjunctival fibrosis and postoperative exacerbation of ocular cicatricial pemphigoid inflammatory activity in 8 eyes, and advanced ankyloblepharon in 7 eyes. The condition of one eye was unchanged. The beneficial effect of grafting was maintained in nine eyes. CONCLUSIONS: The authors' observations indicate that mucous membrane grafting should not be performed when patients have severe keratoconjunctivitis sicca, very advanced ocular cicatricial pemphigoid, or active conjunctival inflammation uncontrolled by immunosuppression. The authors suggest complete control of inflammation before surgery and perioperative treatment with systemic prednisone while maintaining any ongoing immunosuppressive chemotherapy. The selection of alternative surgical approaches is discussed.

Aged↗