Biomedical subjects
Publications and source records attributed to R Scherer.
A 36-year-old woman developed bullous skin lesions which clinically seemed most likely to be dermatitis herpetiformis or bullous pemphigoid. However, histological examinations as well as immunofluorescence and electron microscopic observations substantiated the diagnosis of pemphigus vulgaris.
Coagulation factors and plasma proteins are significantly decreased in patients with hyperdynamic septic shock. Besides the activation of the coagulation system, the endotoxin-induced release of granulocyte proteases is responsible for a septic disseminated intravascular coagulation. In this situation special emphasis should be placed on the levels of antithrombin III regarding application of heparin.
Baby hamster kidney cells fixed in acetone on glass slides were used as antigen for demonstration of antinuclear antibodies. Where certain storage conditions were observed (drying agent, 4 degrees C) they have kept for 12 months up to now. As regards specificity, sensitivity, reproducibility, and differentiation of fluorescent types the baby hamster kidney cell test appears superior to other immunofluorescence methods used (chicken erythrocytes, rat liver sections, and crithidiae). These results were obtained in 73 sera from patients with disseminated lupus erythematodes, drug-induced lupus erythematodes, discoid erythematodes, allergic vasculitis, progressive scleroderma, dermatomyositis, and 36 control sera.
The acute inflammatory rat paw oedema induced by subplantar injection of carrageenan was significantly inhibited by intraperitoneal injection of rat fibrinogen, intraperitoneal and intracardial injection of fibrinoepetides A and B. In contrast the fibrin split products derived from plasmin digestion proved to be ineffective.
1. Spearman's rank correlation coefficient between erythrocyte sedimentation rate and the concentration of twenty individual plasma proteins was determined in 72 persons including 37 patients with recent myocardial infarction. The highest correlation coefficients with ESR could be demonstrated in the following proteins: fibrinogen, alpha-1-acid-glycoprotein, alpha-2-macroglobulin, alpha-1-antitrypsin, coeruloplasmin, Ig M. The closest correlation with ESR was found, when the molar concentrations of fibrinogen, alpha-2-macroglobulin and Ig M were summed up. 2. Subdivision of the examined group of patients according to their diagnosis showed that the degree of correlation with ESR in many plasma proteins essentially depends on the composition of the studied group of patients. The patients with myocardial infarction, with pneumonia and those with neoplasma all showed distinctly different patterns of correlation. These obviously reflect underlying changes in the concentrations of the studied proteins, that seem to be specific to the respective disease. 3. In 4 patients with myocardial infarction the changes in plasma protein concentrations together with ESR were followed over a period of 26 days after the infarction.
1. A typical case of Erythema elevatum diutinum (E.e.d.) with extracellular cholesterosis is described clinically and histologically in a 48-year-old woman. The disease had a course of 15 years. 2. Electron microscopy confirmed the histological and immunfluorescent findings of leucocytoclastic vasculitis. In older lesions, histiocytes/macrophages predominate. Intra- and extracellular lipid depositions showed a variety of ultrastructural characteristics which differed from electron microscopical findings described in other disorders associated with lipid deposition. 3. The findings are in accordance with the hypothesis that the primary event in E.e.d. is a special type of chronic leukocytoclastic vasculitis. Subsequently, the damage of the vessel walls and focal necrosis may lead to secondary lipid deposition.
A leukocytoclastic vasculitis was induced by intracutaneous injection of streptococcal antigen in a patient with erythema elevatum diutinum (E.e.d.). The immunoelectronmicroscopical demonstration of C3 was performed by use of the peroxidase-antiperoxidase multistep technique 24 h after the injection of the antigen. Deposits of C3 were found between endothelial cells, on the outer surface of endothelial cells, pericytes, and smooth muscle cells, as well as within the multilayered basal lamina of small vessels. Intact and disintegrating neutrophils accumulate within the vessel walls and in their surroundings. Necrosis and fibrin deposition are present in advanced stages. The findings demonstrate the sequence of events in leukocytoclastic vasculitis at the ultrastructural level. They also support the hypothesis that in E.e.d. an Arthus type reaction induced by bacterial antigens may be of pathogenetic significance.
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In 4 cases of allergic vasculitis circulating immune complexes (IC) were demonstrated. Spontaneous and histamine induced vascular changes were studied by immunofluorescence microscopy. The early events in IC vasculitis were investigated at the ultrastructural level by immunoelectronmicroscopy using the peroxidase-antiperoxidase multistep technique. Our findings support the concept that human IC vasculitis is triggered by the deposition of circulating IC in the walls of postcapillary venules between endothelial cells, pericytes and the layers of the basal lamina. Tissue destruction is only secondary due to local complement activation and the release of lysosomal enzymes from chemotactically attracted leukocytes.
99mTc-DAIDA is superior to other cholotropic radiopharmaceuticals. As radiochromatographic examinations with various systems showed, it is secreted by the hepatocytes into the bile as an unchanged anion. In a study of hepato-gastroenterologically selected patients (n = 45) values for liver function parameters such as Tmax' T/2, time of appearance in gall-bladder and duodenum were in the group of patients without any hepato-biliary disease (x +/- S.D.): 15.5, +/- 5.2 min, 30.8 +/- 8.2 min, 13.5 +/- 6.1 min, and 22.0 +/- 10.8 min. The clearance determined after comparison of different defining regions and types of calculation in this group was 323.8 +/- 145.8 ml/min x 1.73 m2 (x +/- S.D.); the renal excretion competitive with the hepato-biliary elimination amounted within 51 min p.i. to 5.15% of the injected activity. The values of the several time-parameters as well as the participation of the kidneys in the 99mTc-DAIDA excretion increased substantially in patients with intrahepatic jaundice, but only slightly in the group of other liver cell diseases. It was not possible to determine the various liver function values in patients with extrahepatic jaundice. Because of their large spread within the different groups these parameters were without diagnostic relevance in the individual case. The hepato-biliary sequential scintigraphy with 99mTc-DAIDA appears to find its main use in morphologic diagnostics.
After an acute course of pharyngitis and bronchitis treated with Bactrim (trimethoprim and sulfamethoxazol), a 52 year old woman suddenly developed a widespread, sterile pustular eruption with predilection of the distal parts of the extremities. The histological and electron microscopical examinations showed intraepidermal pustules with underlying distinct leukocytoclastic vasculitis. Direct immunofluorescence revealed the prescence of intra- and perivascular deposits of C3 in the upper part of the dermis. Drug- and/or infection allergy is suggested to be responsible for the etiopathogenetic mechanism of leukocytoclastic vasculitis.
The morphology of PUVA-treated and PHA-stimulated human peripheral lymphocytes in vitro was studied by means of the light and electron microscopes. Most cells showed signs of cytolysis, such as pyknotic nuclei and a swollen and decomposed cytoplasm; a few cells, however, appeared as normal lymphoblasts. In the latter, repair-enzyme mechanisms may successfully have rectified alterations in the DNS prior to the inception of S-phase. These findings are discussed with reference to the in vivo effect of PUVA treatment.
The presence of in vivo bound complement (C3) within the stratum corneum of 4 psoriatic cases is demonstrated ultrastructurally by the use of the peroxidase-antiperoxidase multistep technique. The positive reaction product was located in the intercellular space and on the surface of the parakeratotic cells within the horny layer. The membranes of the horny cells were not altered and peroxidase granules could also not be detected within their cytoplasm. The explanation of this finding as well as its pathogenetic significance is discussed.
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Herpes gestationis occurred in a 26-year-old woman during the last weeks of her second pregnancy. Within 8 days of the delivery the disease had progressed to such an extent that systemic treatment became necessary. Whereas pre-delivery treatment had consisted exclusively of local desinfection, and steroid and antibiotic ointments, treatment after delivery also included systemic use of prednisolone. After treatment for 3 weeks the skin changes had disappeared except for minimal pigmentation. Using immunofluorescent microscopy a complement activation in the dermo-epidermal junction and in adjacent clinically healthy skin could be demonstrated: There were massive linear depositions of C3, C1q and C4. In the basal membrane of the epidermis IgM could be demonstrated as an unusual finding. Further immunopathological features were found in the form of an immune complex vasculitis which could be shown during the active phase of the disease.
The effect of psoralen plus long wavelength ultraviolet light (UVA) on 3H-thymidine uptake of PHA stimulated human lymphocytes was investigated. PHA induced lymphocyte transformation was inhibited by the combined action of psoralen and UVA irradiation in a dose related manner. Inhibition of DNA-synthesis occurred at concentrations of psoralen that can be expected in the serum of patients treated by systemic photochemotherapy. No effect was noted at these psoralen concentrations in the absence of UVA irradiation. Also did UVA irradiation in the absence of psoralen not inhibit 3H-thymidine incorporation into PHA stimulated lymphocytes.
Local inflammatory processes in the human as well as in experimental animals cause a selective increase or decrease of the hepatic synthesis rate of many plasma proteins. The resulting systemic changes in the plasma-protein profile regulate the extent of the local inflammatory response. The physiologic importance of this feedback mechanism is directed at preventing the spread of local inflammatory tissue destruction. By means of mediator substances involved in this regulatory system, the infalmmatory responses can be experimentally manipulated.
Lymphocytes from healthy human donors were used as a model system for studying the combined effect of 8-methoxypsoralen (8-MOP) plus UVA. Two hours after oral administration of therapeutic doses of the drug enough 8-MOP was taken up in vivo by the circulating peripheral lymphocytes to cause significant inhibition of phytohaemagglutinin induced lymphocyte proliferation when the cells were exposed in vitro to UVA irradiation. The inhibition of proliferation as monitored by a reduced 3H-thymidine incorporation into cellular DNA was shown to be UVA-dose dependent. Control cultures of 8-MOP containing lymphocytes which were not UVA irradiated showed normal blast transformation. In lymphocytes obtained from the same donors prior to 8-MOP intake, PHA-induced lymphocyte transformation was not impaired by UVA irradiation. In 8-MOP containing lymphocytes exposed repeatedly to UVA during the 72 h culture period a cumulative effect of irradiation could be observed. A varying sensitivity towards 8-MOP plus UVA was noted when the cells were irradiated at different times after PHA stimulation. The cells were most vulnerable to UVA irradiation during the DNA-synthesis phase of the proliferating lymphocytes. The results suggest that dermal inflammatory infiltrates containing locally proliferating lymphocytes are influenced by systemic photochemotherapy since UVA penetrates well into the dermis.