Serum and urinary aminoterminal type III procollagen peptide in progressive systemic sclerosis: relationship to sclerodermal involvement, serum hyaluronan and urinary collagen metabolites.

Increased serum values of aminoterminal type III procollagen peptide and hyaluronan (hyaluronate) and enhanced urinary content of hydroxyproline and hydroxylsine containing polypeptides were demonstrated in patients with progressive systemic sclerosis (PSS). The serum propeptide level and the relative urinary excretion of hydroxyproline as polypeptides were related to the extent of cutaneous involvement. Elevated serum propeptide and hyaluronan values were seen in patients who progressed within the following 6 months.

Blister spreading, a diagnostic test in pemphigus. Loss of epidermal and dermoepidermal cohesion.

Differentiation of the pemphigus group of diseases from other bullous dermatoses can be established by spreading of blisters by gentle finger pressure. In combination with histopathology, the same test is diagnostic for every single pemphigus disease.

Scleroderma.

After a review of some pathogenetic and pathologic aspects of scleroderma, the experimental effects of a group of agents that can inhibit the formation of connective tissue, especially the biosynthesis of collagen, are mentioned. These substances were transferred to clinical therapy of scleroderma. Regular determinations of disease activity and guidance of therapy with quantitative and semiquantitative physical and biochemical technics are of utmost importance because treatment without guidance allows for no disclosure of therapeutic failure or recurrence of the disease in due time for readjustment of the treatment.

Bioavailability of D-penicillamine in relation to gastrointestinal involvement of generalized scleroderma.

The bioavailability of D-penicillamine was measured in 24 patients with generalized scleroderma (Progressive Systemic Sclerosis, PSS). Esophageal changes characteristic of generalized scleroderma were present in 15 of the patients, and 3 of those patients had duodenal involvements as well. The plasma concentrations of D-penicillamine were measured at 0 h, 1 h, 2 h, and 4 h after an oral dose of 300 mg D-penicillamine.

Bioavailability of D-penicillamine in a patient with gastrointestinal progressive systemic sclerosis.

D-penicillamine pharmacokinetics were studied in a patient with gastrointestinal progressive systemic sclerosis possibly complicated by malabsorption. D-penicillamine bioavailability was examined after oral, duodenal, intravenous and rectal administration. No D-penicillamine was detectable in plasma after administration to the gastrointestinal tract.

Secretion of type IV collagen by keratinocytes of human adult.

Secretion of type IV collagen by keratinocytes was studied by anti-type IV collagen immunoglobulin in pure keratinocyte culture of the human adult. The cultivated keratinocytes secreted type IV collagen into the space between the cell growth and the underlying fixed film of human skin collagen type I. The secreted collagen was accumulated on the cell surface to form junction structures.

Development of polyneuropathy during thalidomide therapy.

Seven patients with prurigo nodularis and one with aphthous stomatitis were given 40-115 g of thalidomide for 1 to 6 years. They all developed a predominantly sensory peripheral neuropathy mainly involving the lower limbs. Five patients had an unpleasant tight feeling around the feet.

Filamentous aggregates of collagen. Ultrastructural evidence for collagen-fibril degradation in situ.

Filamentous aggregates of collagen are distinct structures in the pathological dermis. These aggregates are distinguishable from fibrous long-spacing collagen (in vitro and at biopsy) and the Luse body. The aggregates are produced from dermal collagen fibrils by clostridial collagenase and culture-medium extract, which supposedly contains cellular collagenase at a neutral pH, as well as by organ cultures.

Dermal changes in Ehlers-Danlos syndrome.

Skin biopsies from thirteen patients suffering from Ehlers-Danlos syndrome, including 6 of the mitis type, 4 of the benign hypermobile type, one of the X-linked type, one of the ocular type and one of the periodontitis type, were studied by electron microscopy after routine preparation. Collagen fibrils showed a distorted arrangement of bent, curled or twisted fibrils and thread-like material. Similar changes may be seen in the skin of other hereditary disorders of connective tissue.

Treatment of generalized scleroderma with inhibitors of collagen synthesis.

Clinical evaluation of scleroderma and the urinary excretion of collagen specific amino acids and uronic acid indicate disease activity and have become a guide for treatment. During an experimental search for inhibitors of the synthesis of collagen and ground substance glycosaminoglycans, a few connective-tissue active agents were selected for therapy of scleroderma: D-penicillamine, benzyl-penicillin-diethylamino-ethylester-hydroiodide, L-glutamine, hydralazine, glucocorticoids, dextro-thyroxine, L-dopa, diphenylhydantion, chlorpromazine, and (+) catechine. Treatment for several years was required to bring about an arrest of progression in 89% of the patients, a regression in three-quarters, and subtotal or total recovery in more than 40%.

The ultrastructure of bacterial spores in skin of an Egyptian mummy.

The ultrastructure of bacterial spores found in the skin of an Egyptian mummy was studied. The mummy was embalmed during year 100 to 300 of our era. The bacterial spores showed a characteristic appearance with a core, cortex, coat and exosporium.

Ultrastructure of skin and hair of an Egyptian mummy. Transmission and scanning electron microscopic observations.

The skin of a female Egyptian mummy, embalmed 100-300 A.D., was studied by transmission and scanning electron microscopy.

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 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.

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.

Ultrastructure of Cryptococcus neoformans.

The ultrastructure of C. neoformans was studied in two cases of cutaneous cryptococcosis. Extracellular and intracellular fungi were observed.

[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.

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.

[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.