The human dermis consists of two morphologically different layers. A loose meshwork of thin collagenous fibres is characteristic for the adventitial dermis with includes the papillary and the periadnexal dermis. Thick, coarse collagen bundles are the main feature of the reticular dermis. Two different collagens, type I and type III occur in the dermis as shown previously by biochemical analyses. Antibodies specific for type I collagen or type III collagen and their corresponding precursors were used in indirect immunofluorescence tests to localize the various collagens in frozen sections of normal adult skin. Whereas type I collagen is found in all dermal layers, the main part of type III collagen can be found within the adventitial dermis. Antibodies against the precursor of type I collagen stain only a bandlike region immediately beneath the epidermis. Antibodies against the precursor of type III collagen stain the same regions as antibodies against the helical part of type III collagen.
Antibodies against two types of species specific determinants, designated P and S, can be differentiated in rabbit antisera against acid soluble calf skin collagen. Using the passive bemagglutination inhibition technique, they were localized with collagen a-chains, with peptides obtained by treatment of the a-chains with cyanogen bromide and with fragments isolated from collagenolytic digests of native collagen.The P-determinant is labile to proteolytic attack (pronase, chymotrypsin, pepsin). It was detected in a 300 A region a t the C-terminus of both types of a-chains. The S-determinant is resistant to proteases and was found to occur in an interior region of the a2-chain. The serological activity is contained in one of the collagenolytic peptides.Studies of rabbit antisera to acid soluble calf skin collagen revealed the presence of three major antigenic determinants on the collagen molecule [l]. Two of these determinants were species specific ; they could be demonstrated on calf collagen but not on rabbit collagen. They were distinguished by their sensitivity to proteolytic attack. The species specific P-determinant was destroyed by treatment of the native collagen molecule with proteases such as pepsin, pronase, and chymotrypsin, whereas the species specific S-determinant was resistant to these enzymes. A third, collagen specific A-determinant was found on calf and rabbit as well as on fish and invertebrate collagens and was likewise resistant to proteolytic digestion.Recent progress in the elucidation of the collagen structure furnished a number of well defined peptides that could be evaluated for their antigenic properties. Thus, cyanogen bromide cleavage of calf skin collagen yielded eight peptides from its al-chain and five peptides from the a2-chain. These peptides have been characterized and their respective positions within the a-chains have been established [2-51. Additional information became available when collagen was treated at low temperatures with collagenase from Clostridium histolyticum [6]. This enzyme acts from the ends of the triple helical molecule. By careful control of the experimental conditions a series of different fragments was obtained. These fragments could be characterized by electron microscopy with respect to their length and their positions within the molecule. When they were denatured, their constituent a-chains were obtained. Enzyme. Pepsin (EC 3.4.4.1).-~ Investigations reported here were initiated in order to localize the two species specific determinants P and S of calf skin collagen. The al-and a2-chains, their CB-peptides, and the peptides derived from collagenase treatment were evaluated for their serological activity. The P-determinant was found to reside in C-terminal positions of the molecule, the S-determinant in an interior region of the a2-chain. MATERIAL AND METHODS Acid Soluble CollagenThe corium of calf skin was homogenized and extracted in the cold twice for 24 h with a ten-fold volume of 0.5M sodium acetate. The residue after centrifugation was washed once w...
The collagen in localized and systemic scleroderma skin was studied by light microscopy with silver impregnation (50 patients), electron microscopy (14 patients), and immunofluorescence microscopy using specific antibodies against Type I and Type I11 collagens (12 patients). In the cellular stage, the dermis and adipose tissue revealed perivascular or diffuse cellular infiltrates (mostly lymphocytes, plasma cells, and macrophages), accompanied by deposition of Type I11 collagen. The lower dermis also showed an increase in Type I11 collagen. In the fibrotic stage, the papillary layer showed a reduction and/or clumping of Type I11 collagen as compared to normal skin. The lower dermis and the adipose tissue revealed compact collagen consisting exclusively of Type I collagen or a mixture of Type I and Type 111 collagen. The pattern of Type I11 collagen distribution was similar to that of reticulin, thus suggesting that at least some reticulin fibrils may represent Type I11 collagen.
Compared with the antipsoriatic retinoid etretinate, the new aromatic retinoid acitretin represents an important advance due to its rapid elimination kinetics. Since in psoriasis vulgaris retinoids are used predominantly in combination regimens, we investigated the therapeutic efficacy of acitretin and UV-B compared with placebo and UV-B in a double-blind, randomized multicenter trial in 82 patients with severe psoriasis. They were treated with 35 mg of the study medication during the first 4 weeks of therapy and 25 mg thereafter, concomitantly with UV-B irradiation in increasing energy doses. Forty patients who underwent therapy with acitretin and UV-B and 38 patients who underwent therapy with placebo and UV-B were evaluated for efficacy. The target variables--psoriasis severity index and total UV-B dose--were reported at intervals of 2 weeks over a maximum period of 8 weeks. At the end of treatment, the psoriasis severity index decrease was 79% in the acitretin and UV-B group and 35% in the placebo and UV-B group. The response rate, defined as greater than or equal to a 75% decrease of the psoriasis severity index, was 60% for the combination treatment and only 24% for the control treatment. This treatment response was achieved with markedly lower cumulative UV-B energy. The median cumulative UV-B energy applied to reach 75% clinical improvement was 11.8 J/cm2 vs 6.9 J/cm2. Side effects showed a similar pattern in both groups. Our data show that the acitretin dramatically improves the results of UV-B treatment in patients with severe psoriasis. In addition, it markedly decreases the effective cumulative UV-B dose, thereby reducing the potential long-term hazards of UV irradiation. We conclude that the acitretin plus UV-B combination treatment represents a highly effective therapeutic regimen in severe psoriasis.
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