Kimmo K. Mustakallio

Corticosteroid-induced inhibition of the biosynthesis of human skin collagen☆

Abstract The effects of hydrocortisone acetate, fluocinolone acetonide, fluclorolone acetonide, betamethasone-17-valerate, fluprednyliden-21-acetate and flumethasone pivalate on the biosynthesis of human skin collagen were studied in vitro . Skin specimens were incubated in a medium containing a test substance and radioactive proline, and the formation of radioactive hydroxyproline in nondialysable proteins was taken as an index of the rate of collagen biosynthesis. Hydroxyproline formation was inhibited by all the corticosteroids tested in concentrations of 30 μg/ml or higher. The effect on hydroxyproline formation was smallest with hydrocortisone acetate and most pronounced with betamethasone-17-valerate in all concentrations used. In general, the corticosteroid-induced inhibition of collagen biosynthesis was found to be dose-dependent. The differences in the degree to which collagen formation is inhibited by the different corticosteroids may have relevance to the extent of the local side-effects, such as atrophy of skin, reported to be produced by fluorinated corticosteroids.

Effect of hydrocortisone acetate, fluocinolone acetonide, fluclorolone acetonide, betamethasone-17-valerate and fluprednyliden-21-acetate on collagen biosynthesis

Abstract The effect of hydrocortisone acetate, fluocinolone acetonide, fluclorolone acetonide, betamethasone-17-valerate and fluprednyliden-21-acetate on collagen biosynthesis was studied both in vivo and in vitro . In experiments in vivo , test substances and [ 14 C]proline were injected on the chorioallantoic membrane of 11-day-old chick embryos. In experiments in vivo , chick embryo tibiae were incubated in a medium containing the corticosteroids to be tested and [ 14 C]proline. In both types of experiments, the formation of [ 14 C]hydroxyproline was taken as a measure of the rate of collagen biosynthesis. In addition, the effect of these corticosteroids on the activity of protocollagen proline hydroxylase was tested. [ 14 C]hydroxyproline formation in vivo was inhibited by all the corticosteroids tested, and no clear difference in the degree of inhibition could be observed between the various corticosteroids. in vitro , betamethasone-17-valerate inhibited hydroxyproline formation more than the other substances tested. The concentration of corticosteroids required to inhibit collagen formation was considerably higher in vivo than in vitro . The corticosteroids tested did not affect the activity of protocollagen proline hydroxylase in the bones. In all these experiments, total protein synthesis, measured as incorporation of total 14 C-radioactivity into the bones, was inhibited by corticosteroids to the same extent as hydroxyproline formation. The results seem to suggest that corticosteroids inhibit collagen biosynthesis by inhibiting the formation of polypeptide precursors of collagen.

Histochemistry of Kaposi's sarcoma. I. Hydrolases and phosphorylase☆

Abstract Hydrolases and phosphorylase were demonstrated histochemically in six specimens of Kaposis sarcoma obtained from three patients. The linings of the vascular slits were lacking in alkaline phosphatase activity. The spindle-shaped or stellate cells adjoining the vascular slits showed little or no alkaline phosphatase activity but high unspecific esterase and moderate acid phosphaatase activities. The spindle cells of the compact bundles of the tumor displayed a slight to moderate esterase activity and little or no reaction for phosphatases. All specimens displayed an intense over-all aminopeptidase activity, but no phosphorylase was demonstrable. The authors suggest that the spindle cells of the vascular slits and those of the bundles represent two functional stages of multipotent mesenchymal cells. The former have a “reticulo-endothelial” function, i.e., phagocytosis and formation of reticular fibers; the latter acquire a fibroblastic character.

Some aspects of scleroderma heart disease

Abstract Seven unselected cases of scleroderma were studied electrocardiographically. No marked electrocardiographic abnormalities were found. The alterations, if present, consist of prolongation of P-R, QRS, and Q-T intervals, of slight changes in the configuration of RS-T segments and T waves, and especially of slurring and notching of QRS deflections in multiple leads. These are interpreted as minor conduction defects possibly due to interstitial fibrosis of the myocardium.

Histochemical Demonstration in Rat of Monoamine Oxidase Inhibition by β-Phenyl-Isopropyl Hydrazine

A histochemical method for demonstration of monoamine oxidase activity was found to be almost as sensitive as a biochemical method when used for revealing total inhibition of monoamine oxidase in rat tissues after administration of β-phenyl-isopropyl hydrazine. The histochemical method is of special value in the study of monoamine oxidase inhibition in the complex structures of the brain.

The distribution of quinacrine in Taenia saginata.

Abstract The distribution of quinacrine in six beef tapeworms, Taenia saginata , expelled by this drug has been studied with the aid of a fluorescent microscope. The observation that quinacrine possesses a great affinity for the holdfast organs may be of value in explaining the teniafugal action of quinacrine.

Persistence of characteristic QRS pattern of Wolff-Parkinson-White syndrome in middle nodal rhythm.

Abstract A case of Wolff-Parkinson-White syndrome with prolonged QRS complexes without visible P waves in middle nodal rhythm is presented. An anomalous conduction in the bundle of Mahaim is claimed to be the etiologic explanation in this case.

Histochemistry of Kaposi's sarcoma: II. Cholinesterases, monoamine oxidase, and adenosine triphosphatase

Abstract Skin specimens of three patients suffering from Kaposis sarcoma were studied; use was made of three nerve-staining methods and the histochemical demonstration of acetylcholinesterase, pseudocholinesterase, monoamine oxidase, and adenosine triphosphatase activity. Altogether five tumors were examined, representing the infiltrative as well as the angiomatous and sarcomatous phases of the disease. The observed absence of both cholinesterases and monoamine oxidase activity does not support the hypothesis of a neural origin of the tumors. Adenosine triphosphatase activity was most intense in the peripheral fibrocytes and fibroblasts and in the macrophages inside the tumors. The spindle-shaped tumor cells exhibited varying ATPase activity. Round cells with enzyme distribution characteristic of plasma cells were encountered only occasionally. On the basis of the results presented, it is suggested that the tumor cells of Kaposis sarcoma do not arise from neural cells but rather from multipotent mesenchymal cells, since they display histochemical features indicative of such an origin.

HISTOCHEMICAL STUDIES ON CUTANEOUS LEIOMYOMATOSIS. II: DEHYDROGENASES, HYDROLASES AND PHOSVHORYLASE.

THE differential diagnosis of benign tumours of the dermis may be difficult (cf. Montgomery and Wiiikelmami, 1958) ; e.g. the similarity between the histological appearance of leiomyomas and that of some neurogenic tumours may be such as to give rise to diagnostic difficulty. This is readily understandable in tho light of our previous report on the innervation of cutaneous leiomyomata (Mustakallio et al, 1963) in which it was demonstrated by means of histochemieal techniques that there is considerable proliferation of neural elements in tumours originating from arreetor pili muscles (i)ilomyomata). On the other hand, in recent years histochemieal methods have aLso been developed, which enable musele tissue to be differentiated in a rather specific way. It is the pui-pose of the present communication to report upon a histochemical study wherein several enzyme reactions were used on normal arreetor pili muscles and on pilomyomas in order to discover specific microscopic features which might be of practical differential diagnostic value.

Freie Vorträge, Kreislauforgane

The aortas of feti in the last gestational months, and of newborn babies up to one year of age, were investigated and special attention was paid to mucopolysaccharides of the ground substance. The cases were devided into three groups: normal subjects, cases with congenital malformations of the cardiovascular and other systems, and subjects with infectious diseases.—During the last months of fetal life the aortic wall undergoes continuous changes consisting of increase of the ground substance and of progressive separation of the elastic layers with alterations of their regular parallel disposition. — Maturative processes may be disturbed by infectious diseases which are able to induce changes directly or by means of the endocrine system (adrenal glands) in the ground substance such as focal accumulations of chromo-trope substance in the intima and in the media, destruction of elastic systems and increase of collagen fibers. — The first change in fetal aortic walls due to pathological factors is represented by an alteration in the composition of the ground substance, which appears stained deeper by Alcian-blue on account of an increase of the degree of polymerisation of mucopolysaccharides. — Special importance is attributed to this kind of changes in the aortic wall, before or after birth within the first year of age, and to their possible significance in view of later alterations to which the vessel may undergo in adult life.