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Biomedical subjects

G Asboe-Hansen

Publications and source records attributed to G Asboe-Hansen.

At least 37 records · Page 2Linked to original sources

Desmosome formation in normal human epidermal cell culture.

Keratinocytes were dissociated from normal human adult epidermis with clostridial collagenase, dithio-erythritol and trypsin, and cultured. Immediately after this, no connection was seen between contiguous cells. Ruptured desmosomes, with masses of tonofilaments and distinct attachment plaques were still left on the cell surface. As culture proceeded, however, they became internalized into cytoplasm. As soon as culture was started and the cells established contact with each other, forming conglomerates, they began to form desmosomes. The cell membranes of a limited area which were in contact with neighbouring cells became thicker and formed attachment plaques. In the intercellular space of the desmosomal portion, fine filaments developed and a midline formed. The progress of desmosome formation was classified into six types.

Adhesiveness↗

Acantholysis induced by proteolytic enzymes. I. Porcine pancreatic elastase.

In an attempt to induce acantholysis in cultivated normal human epidermis, porcine pancreatic elastase was used. After 30 minutes, the intercellular contact layers of desmosomes appeared discontinuous. Following the disappearance of the intercellular filamentous structures, desmosomes ruptured into two, and in 3 hours, typical acantholysis was observed. After 15 minutes, prior to the desmosomal changes, dermo-epidermal separation started at the subepidermal space. After 2 hours of elastase influence, anchoring filaments and the basal lamina were degraded. Five hours from the start of culture, the anchoring fibrils remained undigested by elastase. The mechanism of elastase influence on epidermis is assumed to depend rather on its proteolytic activity than on its elastolytic activity.

Acantholysis↗

Acantholysis induced by proteolytic enzymes. II. Enzyme fractions produced by Trichophyton mentagrophytes.

Trichophyton mentagrophytes produces three enzyme fractions of molecular weight 65,000, 92,000 and 18,000, respectively. Normal human skin was cultivated and the specimens were subjected to electron microscopy. Enzyme fraction I showed the capacity to induce epidermal acantholysis and dermo-epidermal separation, while the other two fractions showed no proteolytic nor keratinolytic action in cultivated skin.

Acantholysis↗

Size of desmosomes and hemidesmosomes in normal human epidermis.

The dimensions of desmosomes and hemidesmosomes in normal human epidermis, i.e. their length and thickness, were studied in ordinary ultrathin sections. The length of desmosomes in the inner and middle squamous cell layer was 310 nm and 300 nm, while the thickness was 31 nm and 30 nm, respectively. In the outer squamous cell layer the values increased to 340 nm and 35 nm, respectively. The percentage total desmosomal length in relation to the perimeter of a cell showed the same tendency.

Adult↗

[Granulomatosis disciformis chronica et progressiva (Miescher-Leder)].

A case of granulomatosis disciformis chronica et progressiva in a 75-year-old diabetic is reported. The dermatosis which was successfully treated with a high-potent local steroid preparation, today is regarded as a granulomatous variety of necrobiosis lipoidica. The present case shows, as originally described by Miescher and Leder, that the clinical findings as well as the histopathology represent an entity which may differ markedly from the common type of necrobiosis lipodica.

Aged↗

Variation of urinary acid glycosaminoglycan and collagen metabolite excretion with disease activity in generalized scleroderma.

Follow-up of patients with generalized scleroderma improving during treatment with collagen biosynthesis inhibitors showed a decrease towards normalization of the elevated urinary values for acid glycosaminoglycans and collagen catabolites. The determinations supply objective evidence of the disease activity as well as of the efficacy of treatment. In the control group, relatively high urinary values for the two macromolecules were found in the second decade of life in comparison with older age groups.

Adult↗

Biochemical analysis of dermis and urine in generalized scleroderma.

The urinary excretion of uronic acid and the hydroxyproline of a urinary fraction of high molecular weight collagen peptides (% of total Hyp) indicate disease activity in generalized scleroderma. A significant decrease in the content of Hyp and Hyl in the skin of sclerodermal patients is not related to activity, but rather to the duration of the disease. Parallel analyses of skin and urine of the same patients are reported.

Adult↗

Studies on the effect of (+)catechin on connective tissue in the guinea pig and in organ culture.

Decreased biosynthesis of (14C) hydroxyproline in skin collagen was observed after injection of the flavonoid (+)catechin into guinea pigs. No alteration in already synthesized collagens was noted, as measured by the content of hydroxyproline and hydroxylysine. No alteration in the content of skin acid glycosaminoglycans was observed. The variable binding of (+)catechin to different tissues was demonstrated. No special sensitivity to the drug of any collagen type was found.

Animals↗

[New developments in the pathology, pathophysiology and therapy of systemic scleroderma].

In scleroderma, collagen and elastic fibres as well as the dermo-epidermal junction are pathologic. The reactivity of the blood vessels, the function of the smooth muscle cells and the factors protecting against edema formation are defective. The urinary excretion of metabolites of collagen and ground substance glycosaminoglycans indicates quantitatively disease activity. After experimental mass testing in tissue culture, a group of inhibitors of the biosynthesis of essential connective-tissue components were transferred to therapy of scleroderma. In 89 percent of 115 patients, progression could be arrested. After several years of treatment, a regression came about in 74 percent of which 41 percent was subtotal and 17 percent total.

Amino Acids↗

Effect of hydralazine and dihydralazine on connective tissue and binding to serum protein.

Hydralazine and dihydralazine, chelators of Fe2+, Fe3+ and Mn2+ ions, inhibited collagen biosynthesis in organ culture of chicken embryo tibiae. Both substances inhibited the in vitro hydroxylation of [14C]Pro-labelled protocollagen by protocollagen proline hydroxylase. A decreased incorporation of [14C]-D-glucosamine into glyco- and/or muco-proteins was found under the effect of the two drugs. Dihydralazine, a cationic compound, was bound to DNA and acid mucopolysaccharides (glycosaminoglycans), forming an insoluble complex. Both substances were bound to serum alpha 2-globulin. Subcutaneous injections of dihydralazine in rats produced a local as well as a general toxic effect.

Animals↗

[The dermoepidermal junction in skin diseases].

Dermatological conditions characterized by dermo-epidermal separation, basal lamina discontinuity, multiplication, and thickness variability, and/or irregularity of the subepidermal space are discribed. Pathological changes of the dermo-epidermal junction are considered to be destructive or reproductive. Both may appear in combination. Destructive processes may be relfected by dermo-epidermal separation. Epidermal cells and/or dermal connective tissue appear degenerated. Thickening of the lamina may occur by reactive hyperproduction or by precipitation of pathological materials. Reproductive processes of the junction originate in the epidermal cells and are reflected in multilayering of the basal lamina. Interruption of the lamina and irregularity of the subepidermal space often precede these phenomena.

Dermatitis↗

Urinary proline to hydroxyproline ratio varies with age.

Urinary excretion of proline and hydroxyproline was studied in five groups of subjects, viz. controls, pituitary dwarfs, familial dwarfs, patients with fibrodysplasia ossificans progressive and patients with generalized scleroderma. The ratio Pro/Hyp in the urinary fraction precipitated with 5 parts of acetone (1 + 5 fraction) was close to one in children and youngsters in all the groups, while in adults it was higher than two. Total Pro/Hyp does not give an accurate index of age.

Adolescent↗

Ultrastructure of skin in primary systemic amyloidosis.

Amyloid masses were found in the dermis of two brothers suffering from primary amyloidosis. The masses consisted of fibrils, composed in turn of twin hollow filaments of amyloid. An amyloid filament appeared as a 3 nm thick lucent core with a 2 nm thick wall. Occasionally 4--6 filaments were packed together in one fibril. The twin filaments were slightly twisted, with a twisting angle of 2.5 degrees and a coiling pitch of 1 160 nm. Wavy shapes of amyloid fibrils were also seen in elastic fibres. Amyloid fibrils were found in elastic fibres, under the basal lamina of the epidermis, sweat gland epithelium and Schwann cells; also around perineural cells, perivascular cells and, in one of the brothers, in collagen fibril bundles. No amyloid fibrils were found under the endothelial basal lamina. It would appear that amyloid fibrils are pathological fibrils belonging to the elastic fibre-basal lamina system.

Aged↗

Treatment of generalized scleroderma: updated results.

Long-term treatment of patients with generalized progressive scleroderma by means of inhibitors of connective-tissue biosynthesis brings about total or subtotal regression of dermal sclerosis in 40.8%, partial regression in 33.1%, arrest of progression without regression in 14.8%, while in 11.3% it had no effect whatsoever. The drugs used were D-penicillamine, benzyl-penicillin-diethyl-aminoethylesterhydro-iodide, glutamine, hydralazine, chlorpromazine, L-dopa, diphenylhydantoin, and corticosteroids. Disease activity before, during and after treatment was indicated by the urinary fractions of high-molecular hydroxyproline and hydroxylysine containing peptides and of uronic acid, break-down products of collagen and acid glycosaminoglycans of connective-tissue ground substance. The prospects were better for young patients than for old, for those with a short history than for the longstanding disease cases, and for those having a large total dose than for those who had less. If left untreated, scleroderma progresses inexorably.

Chlorpromazine↗

Fibrodysplasia (myositis) ossificans progressiva treated with disodium etidronate.

Two patients with fibrodysplasia ossificans progressiva (FOP) were treated with disodium etidronate, a disodium salt of ethane-1-hydroxy-1, 1-diphosphonic acid (EHPD) for two years; both had multiple ectopic ossifications of connective tissue. Regular follow-up showed no improvement in joint movement whilst laboratory examination revealed an increase in the serum phosphorus level. Serum calcium and urinary phosphorus excretion remained within normal limits. The urinary calcium excretion varied with the dose of EHDP. X-ray examination showed significant reduction in size and density of the ectopic ossifications, while the density of bones during and after EHDP therapy remained normal. Development of new ossification was inhibited in the active phase of the disease. Suspected side-effects of the drug were occult blood in stools, skin petechiae, and amenorrhoea. Previous reports on the EHDP treatment of disorders with ectopic ossification are summarised.

Adult↗