Aortic protocollagen proline hydroxylase.
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Biomedical subjects
Publications and source records attributed to K Grasedyck.
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The most important effect of penicillamine on collagen metabolism is the reduction of collagen crosslinking. However, even after long time application of penicillamine, collagen is crosslinked to a certain degree. After intravenous injection of a trace dose of (14C) labelled D-penicillamine it can be determined that this substance is rapidly bound to neutral salt soluble, acetic acid soluble and urea soluble collagen fractions and to a lesser extent to insoluble collagen as well. The amount of penicillamine which binds to any of the collagen fractions depends on the turnover rate. When different tissues are compared, penicillamine seems to have the greatest affinity to tissues with a high collagen turnover. Further studies of neutral salt soluble collagen by CM-cellulose chromatography revealed a stable linkage of penicillamine to collagen alpha chains.
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Light-microscopically there are no significant age-dependent changes in the liver, due to the slight increase in biochemically determined connective tissue components. Electron-microscopical comparison of young and old animals show a larger size and decreased numbers of liver cell mitochondria in older animals. Collagen synthesis in liver is accelerated during growth, as demonstrated by assay of the [3H] proline incorporation rates and of the specific activity of hydroxyproline, corresponding to a decrease in the prolyl hydroxylase activity with age. The neutral salt-soluble collagen fraction may be regarded as a parameter for collagen synthesis, which is activated during the growth period and then remains constant without age and sex differences. Not much is known about the significance of these changes with increasing age or about their initiating factors, although there are parallel findings for liver intoxication and inflammation.
Auranofin has no influence on axial skeleton manifestation of ankylosing spondylitis, neither on clinical complaints, nor on function and inflammatory parameters. Peripheral arthritis is possibly influenced positively, but this cannot be stated definitely because of the low number of cases in this study. This question must be analyzed in larger collectives, as alternatives to conventional therapy are needed for the treatment of peripheral joint involvement of ankylosing spondylitis.
Commonly-used serological methods for the determination of Yersinia antibodies are based on the presence of agglutinins, which are frequently absent or of low titer when arthritis begins. Stool cultures are usually negative at that time, so many Yersinia infections are underdiagnosed. On the other hand, significant agglutinin titers, of diagnostic value, become frequently minimised because of cross reactivity with Yersinia and other gram-negative bacteria. With the immunoblot-technique, using specific virulence-associated antigens and the detection of class-specific antibodies, clear statements are possible about whether there is a recent or an old Yersinia infection. As Yersinia arthritis may have an acute start and a protracted course over months, an exact diagnosis is essential for therapy and prognosis, as well as for answering the question of whether there is acute exacerbation of a preexisting rheumatoid illness of an additional infectious arthritis.
The clinically relevant morphological changes of the skin during aging can be summarized by the term "senile atrophy". The changes are a diminished thickness of epidermis with a reduced mitosis rate of epidermal basal cells, shortened and attenuated rete ridges, reduction of epidermal appendages, and a decreased number of fibroblasts and capillaries in the dermis. Corresponding to these morphological findings regarding the cell number in the senile skin (cutis) we found a slight decrease in the DNA concentration of human and rat cutis. The specific DNA activity (3H-thymidine incorporation rate related to DNA concentration) decreased in presenile versus adult animals. The mesenchymal changes in the dermis have been morphologically described by the term "senile elastosis" or "elastoid collagen degeneration", but in fact they correspond to a progressive collagen denaturation with aging. The total collagen concentration, here determined as the hydroxyproline concentration in the human cutis, shows almost constant values from the 3rd until the 9th decade of life in both sexes. This is also true for the skin of two different rat strains. The insoluble collagen fraction shows a relative increase to the disadvantage of the soluble collagen fractions, which can be interpreted as an indicator of a decelerated collagen turnover. In spite of the decelerated turnover, i.e. a prolonged half-life of the collagen metabolism in the skin, the indicators of the collagen neosynthesis (14C-proline incorporation rate, specific hydroxyproline activity, prolyl-hydroxylase activity) are significantly elevated in the cutis of presenile versus adult rats. Any connection of these findings with a possible change in the distribution of collagen types in the senile skin (e.g. pericapillar fibrosis with increase of collagen type I as well as changes in the distribution of type I, III, IV and V) can only be discussed at present. The glycosaminoglycans in the cutis show a minimal increase of the total content of hexosamines and uronic acids with a significant shift in the ratio of the glycosaminoglycan components in favour of dermatan sulfate and keratan sulfate and to the disadvantage of hyaluronic acid and partly also of chondroitin-4-sulfate and -6-sulfate. The neosynthesis of sulfated glycosaminoglycans (indicator method: 35S-sulfate incorporation rate) is only slightly increased whereas the enzyme activities being specific for the glycosaminoglycan catabolism (beta-glucuronidase, beta-N-acetyl-glucosaminidase) are significantly decreased with aging of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)
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