8-Methoxypsoralen acts on lymphocyte membranes in the dark.
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Biomedical subjects
Publications and source records attributed to U F Haustein.
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Total RNA was extracted from skin biopsies of nine patients suffering from systemic sclerosis (SSc). Steady-state mRNA levels of collagen alpha 1(I) and alpha 1(III), collagenase, fibronectin, and beta-actin were studied using specific cDNA probes and compared to those of 12 sex- and age-matched healthy individuals. There was a more than three-fold elevation of collagen I mRNA levels in SSc skin compared to controls. No difference was found, however, for collagen III, collagenase, and fibronectin mRNA levels in SSc and control biopsies. The selective increase of collagen alpha 1(I) mRNA levels indicates a specific alteration of fibroblast metabolism in scleroderma. Analysis of mRNA levels in skin biopsies might not only offer a direct approach to the understanding of the pathophysiology of SSc, but also facilitate the monitoring of fibrotic activity in SSc patients during therapeutic trials.
Angiosarcoma of the face and scalp developed in 12 patients. The patients were five women and seven men with an average age of 71 years. Initial features were solitary or multiple violaceous vascular nodules or plaques. The clinical course was complicated by ulceration, secondary infection, bleeding, anemia, infiltration into the underlying bones, tumor cachexia, and death. Metastases were not observed. Histologically, seemingly benign hemangiomatous capillary-like structures were found in some areas of the tumors, with richly cellular, solid sarcomatous proliferations in other areas. Early and extensive surgical excision is the therapy of choice, but generally it does not alter the relentless course of the disease. Neither palliative radiation therapy nor polychemotherapy is capable of interfering with tumor progression.
8-Methoxypsoralen (8-MOP) serum levels of psoriatic patients poorly responsive to photochemotherapy (PUVA) treatment (problem cases) were determined by the HPLC method with 11 single blood probes over 8 hours. Abnormally low or deviated serum levels were found in 7 of 11 PUVA problem patients. There was a great interindividually different first-pass effect for 8-MOP in dependence on the galenic formulation of the 8-MOP brand; therefore, the change to another 8-MOP brand with a modern galenic formulation led only to a slight increase of serum levels, and consequently an increase in the 8-MOP dosage was necessary. It is important to be cautious at this point because patients may show an unproportional increase of 8-MOP serum levels due to the individually limited capacity of biotransformation. The studies of the authors reaffirm the necessity of the determination of 8-MOP serum levels in problem cases of PUVA therapy.
The frequency of HLA-class I and DR antigen frequencies were studied in 38 (class I) and 19 (DR) patients with bullous pemphigoid, respectively, and compared with controls. There was no important difference in the frequency of HLA-A,B,C, and DR antigens between patients and controls. An increase in the HLA-B7 frequency in poor responders to immunosuppressants (50% vs. 27% in the control group and vs. 13% in the group of all patients) was noticed, and the possible role of this antigen as a marker for poor responders to therapy was suggested.
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Psoriasis, a widespread genodermatosis in Homo sapiens, also appears in primates. We report on a female chimpanzee in Leipzig Zoo. After years of captivity the animal developed erythematosquamous, highly hyperkeratotic, lesions, some confluent, on the knees, elbows, back of the hands and feet and on the forearms and the seat, which showed histologically characteristic features of psoriasis. It may be that both previous infections and psychic stress resulting from social isolation had caused eruption of the disease. In the literature single cases of psoriasiform dermatoses have also been described in other species of monkeys and even in a springer spaniel. Nonetheless, the search for an animal model of psoriasis vulgaris is still going on.
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The stages of human immunodeficiency viruses (HIV) life cycle are described as guide to therapeutic intervention. Practical therapeutic recommendations are given. They should be directed to viruses as the causal agent and to the features of opportunistic infections as well as of associated malignant tumors. Recently 3 progresses could be reached: (1) the application of azidothymidine in the latency phase, when the number of CD4 positive cells decreases below 500/mm3, whereby the progression of the disease can be delayed and side-effects can be reduced; (2) the prophylaxis of pneumocystis carinii pneumonia by inhalation of pentamidin; and (3) the introduction of fluconazole acting against yeast fungus infection, whereby development of resistant yeast strains is still missing and side-effects are smaller than with other antimycotics. In addition, the application of HIV-vaccine in already HIV-infected persons seems to be effective. By combining several drugs their toxicity is to be reduced. Interdisciplinary research and good cooperation among clinicians are conditions for an effective therapy. Last but not least psychosocial aspects and a good psychological guidance and counseling of the affected persons should be considered.
Principal elements of the HIV- and AIDS-prevention in the social field and health care are discussed. The infection with HIV as a sexually transmitted disease can only be prevented by personal caution in the sexual behavior. Counselling should in particular be addressed to risk groups such as homosexuals and drug abusers early enough and contribute to practising safer sex. General rules of behavior and of the hygienics in hospitals are described. The risk of infection by blood transfusion is relatively low, namely 1:300,000 to 1:3 Mio. The modalities of optional anonymous epidemiologic system of registration (report, testing, counselling, care) are discussed. Finally problems of the development of a HIV-vaccine are described, and the necessity to avoid discriminations of HIV infected or endangered persons is underlined.
The history and development of pyrethrum, the natural pyrethrins and synthetic pyrethroids and their insecticidal properties, chemical structure and toxic and allergic side-effects are reported. Permethrin is stressed as a photostable insecticide that is very effective against a large variety of insects and mites with low mammalian toxicity and virtually no allergic side-effects. Only 10-20 min after application, permethrin (1% cream rinse or 0.5% in ethanol) proved to be safe, reliable and cosmetically acceptable in the treatment of infestations with head lice and the prevention of reinfestations, and also in failures with lindane owing to the development of tolerance in the lice. The same was true of 5% permethrin cream (2.5% in children below 5 years of age) used in the treatment of scabies. Permethrin is absorbed percutaneously in only small amounts, is metabolized rapidly in the skin and excreted in the urine. A single "head to toe" application is ideal for eradication programmes allowing lice to be targetted and the prevalence of secondary bacterial infections decreased at the same time. Benzyl benzoate has an irritant potential, and lindane has been reported to exert CNS toxicity in a few anecdotal cases, in particular in small children or after repeated applications in patients with scabies crustosa, and permethrin was distinctly superior to both of these. This is documented by the results obtained in the treatment of 48 children and 56 adults suffering from scabies. Permethrin is recommended in scabies therapy in premature infants, small children, patients with seizures and neurological complications, in treatment failures with lindane entailing the need to repeat the therapy, in scabies crustosa and in pregnant women and nursing mothers.
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Expression of interleukin-2 (IL2) receptors was studied on peripheral blood lymphocytes (PBLs) in 25 patients with bullous pemphigoid. Analysis was carried out by flow cytometry. Without immunosuppressive therapy expression of IL2 receptors only on T cells (CD5) was significantly increased as shown by double staining (11.9% +/- 7.8% vs 2.1% +/- 1% in controls). After 2-3 weeks under immunosuppressive treatment with prednisolone and azathioprine, however, BP lymphocytes did not exhibit any IL2 receptors. PBLs of 18 BP patients showed an increase in IL2 production (1027.4 +/- 670.5 U/ml vs 270 +/- 100 U/ml in controls) during the acute stage of the disease after stimulation with phytohaemagglutinin (PHA)/phorbol myristate acetate (PMA). On the contrary, IL2 production of the same cells in five patients was only in the lowest range of control values after PHA stimulation without PMA (12.5 +/- 29.6 U/ml vs 40 +/- 20 U/ml in controls). Under treatment with immunosuppressants the IL2 production normalized after PHA/PMA stimulation and slightly decreased following PHA stimulation. From these results we conclude that a T-cell activation via activation antigens, as IL2 receptors, and the production of the specific ligand, IL2, may play a role in the pathogenesis of bullous pemphigoid, especially in the earliest stages, and serve as a marker of disease activity.
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In a survey done in East Germany between 1981 and 1988, we found that 93 of 120 male scleroderma patients had long-term exposure to silica dust. We describe our findings in 12 patients with scleroderma and silicosis. The exposure time to silica dust was between 3 and 34 years; the interval between the beginning of exposure and the onset of scleroderma averaged 27.3 years (range 9 to 40 years). Antinuclear antibodies in titers between 80 and 10,240 with nucleolar and/or speckled patterns were found in 10 patients, antibodies against double-stranded DNA in three, Scl-70 (topoisomerase I) in three, and anticentromere antibodies in five. The following markers of collagen metabolism were increased in serum: beta-galactosidase in 12 patients, laminin peptide-P1 in 10 patients, N-terminal procollagen type III peptide in 10, and urinary sialic acid excretion in 7. We propose that crystalline particles of silica less than 5 microns may be phagocytosed by macrophages and release lymphokines and monokines, which activate fibroblasts and enhance their collagen and glycosaminoglycan synthesis. In addition, silica may act as an adjuvant to increase immune reactivity.
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A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.
To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.