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Biomedical subjects

J U Prause

Publications and source records attributed to J U Prause.

At least 37 records · Page 2Linked to original sources

Haematopathology of 'Sjögren-mice': histopathological changes in spleens after semiallogeneic cell transfer.

Haematopoietic transplantation chimeras may be readily produced in adult mice, using F1-hybrids of selected inbred strains as recipients and mice from one of the parental strains as donors. We transplanted spleen cells from BALB/c donors into nonirradiateded F1-hybrids of BALB/c and CBA/H-T6. Both female and male recipients developed a primary Sjögren's syndrome-like exocrinopathy without signs of kidney disease. At long-term follow-up, 7(1/2) months after cell transfer, lymph nodes were enlarged, and spleens were diminished and irregular in shape. In general, changes in haematopoietic organs were more prominent in males. The results verify that although hybrid mice of either sex develop glandular manifestations comparable with primary Sjögren's syndrome, when the immune system is stimulated by semiallogeneic immunocytes, the evoked reactions in haematopoietic tissues show gender difference.

Animals↗

Effects of transpupillary thermotherapy on immunological parameters and apoptosis in a case of primary uveal melanoma.

Transpupillary thermotherapy (TTT) is a new treatment modality for uveal melanoma. We studied whether application of TTT influences the immunogenicity of the tumour cells in vivo or the expression of molecules related to apoptosis. Immunohistochemistry using monoclonal antibodies directed against HLA molecules, HMB45, P53, Fas ligand (FasL), Fas, Bcl-2 and tumour-infiltrating cells was applied to sections of an enucleated eye containing a uveal melanoma that received TTT 1 week before enucleation. The innermost part of the tumour which had been exposed directly to the laser treatment showed no staining for HLA antigens, nor for Fas or FasL epitopes. The intermediate part of the tumour showed a wet necrosis and HLA expression similar to the expression in the peripheral tumour. A large number of macrophages were observed in the necrotic as well as the intact tumour tissue, especially bordering the wet necrotic area. FasL and Bcl-2 were only expressed in the viable, outer part of the tumour. This immunological evaluation of one case of uveal melanoma treated with TTT revealed that TTT may not only have a direct destructive effect on the primary tumour, but may also influence the immunogenicity of uveal melanoma cells, induce infiltration of macrophages into the tumour, and induce apoptosis. The presence of many macrophages suggests that they play a role in the removal of the TTT-treated tumour tissue by phagocytosis.

Adult↗

[Conjunctival nevi in Denmark 1960-1980. A 21-year follow-up].

The clinicopathological characteristics of 343 naevi of the conjunctiva were studied. A significant increase in the number of naevi excised per year was observed. This may have been caused by an increased exposure to actinic rays. An approximately even distribution was found between the three main locations: caruncle, limbal area and eye ball. Intrastromal naevi were excised at a higher median age than compound naevi, and the lowest median age at excision was for junction naevi, which is in accordance with the known histopathological nature of naevi. Recurrence occurred in nine patients (2.7%), and one had transformed into a malignant melanoma. Eight of the recurring naevi were located in the limbal area. Eight of the nine patients were women, suggesting hormonal factors as a possible cause. Recommendations for the handling of conjunctival naevi are given, based on the present findings and on previous reports.

Adolescent↗

The healing effect of all-trans retinoic acid on epithelial corneal abrasions in rabbits.

PURPOSE: The aim of the study was to investigate the possible healing effect of the vitamin A analogue all-trans retinoic acid 0.05% (RA) in vaseline on epithelial corneal abrasions in 13 ocularly healthy Copenhagen white rabbits. METHODS: A corneal abrasion with a diameter of 6 mm was created centrally in both eyes with a trephine and subsequent rubbing off of the corneal epithelium with an n-heptanol soaked swab The corneal abrasions were treated twice daily with topical applications (50 microl); RA was placed in the right inferior fornix and its vaseline vehicle in the left inferior fornix. Photographic documentation of fluorescein stained, non-healed areas, was performed at time points 0, 12, 24, 36, 48 and 72 h. The rabbits were sacrificed by an overdose of pentobarbital and enucleated. Planimetry was performed from corneal photographs. RESULTS: Healed epithelial mean area at time point 36 h was significantly higher after RA compared to vehicle (p=0.036, paired t-test). Median time to 75% and 85% healing was significantly shorter for RA compared to vehicle (p= 0.03 and 0.02, log rank-test). No morphological difference, evaluated by light microscopy (hematoxylin-eosin) or scanning electron microscopy, was noted between the two treatments. CONCLUSION: It is concluded that RA 0.05% applied twice daily increases the healing rate compared to vaseline vehicle.

Administration, Topical↗

Leiomyoma of the caruncle.

A 43-year-old Caucasian male, presented with a swelling of the left caruncle which had persisted for more than ten years. Clinical examination showed a small, smooth, not painful 2x2x2 mm tumor located at the caruncle. There were no signs of orbital involvement. Histologically, the tumor was composed of interlacing fascicles of spindle-shaped cells with bright eosinophilic cytoplasm and cigar-shaped nuclei. Mitotic activity was not observed and the tumor showed no atypia or pleomorphism. The tumor cells reacted with the reticulum stain and Masson trichrome. Immunohistochemically, the tumor cells were positive for vimentin, SMA, MSA, CD34, laminin and a scattered number for S-100. The tumor was classified as a leiomyoma of the caruncle and is the first described in this localisation. The origin of the tumor is discussed.

Actins↗

Rational drug therapy recommendations for the treatment of patients with Sjögren's syndrome.

The aetiology of Sjögren's syndrome (SS) is unknown, and consequently curative treatments are not available. The immunopathogenesis of SS is partly clarified and immune-regulating drugs (IR) may therefore be of therapeutic value. However, the present understanding of SS is still too unclear to allow an exact and evidence-based algorithm for therapeutic decision making. Rational drug recommendations for the therapy of SS must, therefore, rely mostly on empirical data. Several IR drugs have been shown to be able to downregulate the immunopathological activity of primary SS, but it is not certain whether the diagnostic and cardinal manifestations from the eyes and mouth can be improved. In primary SS the disease-modifying qualities of IR and cytotoxic drugs, therefore, largely apply to the treatment of severe internal organ involvement, inflammatory vascular disease and malignant B lymphocyte disease. In secondary SS the IR therapy is directed against the basic immunoinflammatory connective tissue disease. Symptom-modifying therapies include drugs to stimulate and substitute for exocrine functions, and drugs to treat complications of the exocrine disease manifestations and to improve the various nonexocrine disease manifestations. The main drugs available for increasing lacrimal and salivary gland output are bromhexine and pilocarpine, respectively. However, exocrine substitutes, and in particular eye drops, are still the most important means of alleviating the sicca symptoms. They are also indispensable local treatment measures which may help to prevent mucosal complications.

Adjuvants, Immunologic↗

Human retinal pigment epithelial cell-induced apoptosis in activated T cells.

PURPOSE: The immune privilege of the eye has been thought to be dependent on physical barriers and absence of lymphatic vessels. However, the immune privilege may also involve active immunologic processes, as recent studies have indicated. The purpose of the present study was to investigate whether human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which block alloactivation, had no inhibitory effect on RPE-mediated T-cell apoptotic responses in MHC class II-specific CD4+ T-cell lines. CONCLUSIONS: Retinal pigment epithelial cells express FasL and induce TCR-independent apoptosis in activated human T cells through Fas-FasL interaction. Retinal pigment epithelial cells may constitute an immunologic functional barrier against potentially harmful T cells.

Apoptosis↗

Anophthalmia-microphthalmia-oblique clefting syndrome: confirmation of the Fryns anophthalmia syndrome.

We describe a patient with bilateral extreme microphthalmia with bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis. The cause is unknown, but the phenotype resembles the Fryns anophthalmia-plus syndrome, which may be a recessive trait, although intrauterine environmental factors cannot be excluded.

Abnormalities, Multiple↗

Transvitreal retino-choroidal biopsy of suspected malignant lesions of the choroid. Follow-up of cases over 7 years.

The cases of transvitreal retino-choroidal (TVRC) biopsy from 1987 to 1994 were assembled in order to examine the efficiency, complications and risks to patients. Of 92 biopsies 91 had sufficient material for diagnosis. Eighty (87%) contained malignant tissue, whereas 10 cases were negative and two unsuccessful. Tumours of appropriate size were treated by brachytherapy. Twenty-three large tumours were enucleated primarily. Eight irradiated eyes had to be removed. In 31 cases, therefore, it was possible to examine the whole tumour for changes caused by the biopsy and to compare the typing of the biopsy with that of the whole tumour. In the irradiated eyes histologically viable tumour cells remained mostly in the inner part of the tumour. Scleral necrosis was not found. The technique used appears to be safe. Histological verification is highly recommended before any conservative therapy, inter alia to obtain true statistics of therapeutic results.

Adolescent↗

Quantitative assessment of clinical disease status in primary Sjögren's syndrome. A cross-sectional study using a new classification model.

Quantitative and qualitative assessment of the clinical disease manifestations in 41 primary Sjögren's syndrome (pSS) patients was performed according to a new classification model. Frequencies of subgrouped disease manifestations were as follows: 1) surface exocrine disease: 100%, 2) internal organ exocrine disease: 63%, 3) monoclonal B lymphocyte disease: 5%, 4) inflammatory vascular disease: 71%, 5) non-inflammatory vascular disease: 59%, 6) mediator induced disease: 98%. Summary scores for severity of surface exocrine disease correlated to the summary scores of all other disease manifestations (p = 0.02), to the summary scores of internal organ exocrine disease (p = 0.003), and to the summary scores of mediator induced disease (p = 0.03). Blood leucocyte counts showed significant negative correlations to levels of plasma IgG, serum IgA-RF, IgM-RF, anti-SSA/SSB antibodies, IL-6, and IL-1Ra. We conclude that the model made detailed analysis of the clinical presentation of pSS possible, and thus may assist in elucidating important pathobiological aspect of the disease.

Adult↗

[Epiphora].

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Dacryocystorhinostomy↗

Malignant melanoma of the conjunctiva: occurrence and survival following surgery and radiotherapy in a Danish population.

PURPOSE: To describe patient characteristics, risk of recurrence, and survival in patients with premalignant and malignant melanocytic lesions of the conjunctiva. METHODS: In a retrospective study, 55 cases with a minimum follow-up of 10 years were reviewed. RESULTS: The actuarial 5-and 10-year survival rates were 86% (95% Cl: 76-96%) and 73% (95% Cl: 60-87%) respectively. The 5-year risk of local recurrence was 35% (95% Cl: 21-49%), and the 10-year risk was 43% (95% Cl: 28-58%). Primary acquired melanosis with atypia was the first manifestation in 13 cases, malignant melanoma in 42 cases. No significant difference in survival and recurrence was found between the two groups or by gender, location of primary lesion, histological characteristics, or extent of surgical procedure. A minimum incidence of 0.052 cases a year per 100 000 in Denmark was calculated. CONCLUSION: The results are estimated to represent a nationwide sample of patients. No prognostic factors of significance were identified.

Adolescent↗

A bioavailability comparison in rabbits after a single topical ocular application of prednisolone acetate formulated as a high-viscosity gel and as an aqueous suspension.

To increase contact time between drug and ocular surface and thus improve the bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). The drugs were applied to Copenhagen white rabbits as a single application. We compared the bioavailability of prednisolone acetate 0.5% in Leogel with fusidic acid 1% after 1, 4, 7 and 10 h (n = 3 at each time points) with that obtained when doubling the prednisolone acetate concentration in unchanged Leogel and fusidic acid 1% in 12 rabbits. In addition we compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle after 0.5, 1, 1.5, 2, 3, 6, 8 and 12 h (n = 6 at each time points) in 54 rabbits. When doubling the prednisolone acetate dose an increase in bioavailability was achieved in conjunctiva, cornea and aqueous humour with 1.57, 3.86 and 2.18 times, respectively. Prednisolone concentrations in cornea, conjunctiva and aqueous humour were higher using the Leogel vehicle than using the aqueous suspension. The bioavailability in 0-12 h for prednisolone acetate in Leogel and fusidic acid 1% to conjunctiva was significantly higher (p = 0.003) than for prednisolone acetate in aqueous and sulfacetamide sodium 10%. The bioavailability (0-6 h) for conjunctiva was significantly higher for the Leogel preparation than for the aqueous suspension (p < 0.001). For cornea and aqueous humour, the bioavailability values for the total period (0-12 h) do not differ significantly. However, for the first 6 h the difference is significant (p < 0.001 for cornea and p = 0.003 for aqueous humour).

Administration, Topical↗

An ocular bioavailability comparison in rabbits of prednisolone acetate after repeated topical applications formulated as a high-viscosity gel and as an aqueous suspension.

To increase contact time between drug and ocular surface and thus improve the ocular bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). We compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle. We applied the drugs to Copenhagen white rabbits as repeated topical applications (gel preparation: twice daily; aqueous preparation: four times daily) for one week. Dosis regimen was chosen according to earlier investigations (Johansen et al. 1995). Prednisolone concentrations in cornea, conjunctiva and aqueous humour were shown to be higher using the Leogel vehicle than using the aqueous suspension. Fusidic acid and sulfacetamide sodium values were compared with values from a single application (Johansen et al. 1995). Fusidic acid reached higher concentration levels in cornea, conjunctiva and aqueous humour after repeated applications than after a single application. Sulfacetamide sodium concentrations did not rise when applied four times daily for one week. Leogel increases the ocular bioavailability of substance(s) in the gel and allows lower drug concentrations and/or application frequencies.

Administration, Topical↗

Cranio-orbital teratoma.

A new-born baby presented with a large, rapidly growing tumour. The tumour involved the right orbit, the anterior half of the right intracranial space and extended through the skull of the temporal region. The proptotic eye ruptured due to exposure. The tumour was extirpated when the patient was 12 days old. A large recurrence was extirpated two months later. The tumour was firmly bound to the medial aspect of the superior orbital fissure which probably was the location of origin of the tumour. Based on the size of the intracranial-and the orbital part of the tumour, it was classified as a secondary orbital teratoma. The tumour was macroscopically composed of cystic and solid areas. Microscopically it was seen to be a benign teratoma with tissue from all three germinal layers.

Brain Neoplasms↗

Don't cry.

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Animals↗

Conjunctival naevi in Denmark 1960-1980. A 21-year follow-up study.

The clinicopathological characteristics of 343 naevi of the conjunctiva were studied. A significant increase in the number of naevi excised per annum was observed. This may have been caused by an increased exposure to actinic rays. Approximately even distribution in the three main locations: caruncle, limbal area and eyeball, was found. Intrastromal naevi were excised at a higher median age than compound naevi, and the lowest observed median age at excision was for junction naevi, which is in accordance with the known histopathological nature of naevi. Recurrence occurred in nine patients (2.7%), and one transformed to a malignant melanoma. Eight of the recurring naevi were located in the limbal area. Eight of the nine patients were women, suggesting hormonal factors as a possible cause. Recommendations for the handling of conjunctival naevi are given, based on the present findings and on previous reports.

Adolescent↗