Role of specific membrane receptors in urokinase-dependent migration of human keratinocytes.

On the basis of both 125I-labeled plasminogen activator binding analysis and transmission electron microscopy studies of the interaction of a plasminogen activator/gold complex with cell membranes, we have found that human keratinocytes have specific receptors for human urokinase-type plasminogen activator distributed on the cell surface as singlets, or as small or large clusters. The use in binding experiments of the purified A chain of urokinase-plasminogen activator and of anti-A chain monoclonal antibodies has indicated that cell receptors are specific for a sequence present on the A chain, as previously reported for other cells. The interaction of both the native molecule and the purified A chain with such receptors stimulates mobilization of keratinocytes in an in vitro cell model system (Boyden chamber), when present in the lower compartment of the migration apparatus in nanomolar concentrations. Preincubation of chemoattractants with a monoclonal antibody which prevents receptor/ligand interaction also prevents plasminogen activator-induced cell migration. These data suggest that, under the conditions used in this in vitro model system, the plasminogen activator-dependent mobilization of keratinocytes depends on the interaction of the ligand with free receptors on the cell surface, and is independent of plasmin generation.

Steroids versus nonsteroids in the treatment of cutaneous inflammation: therapeutic modalities for office use.

Inflammatory skin diseases are often treated successfully with topical substances alone. The basic prerequisites for proper treatment are that the specialist has a good knowledge of the products available, their active substances and bases and their relative properties and actions, as well as precise indications for and effects of long-term use. Treatment should be individualized, and best results are usually achieved with a two-phase schedule, beginning mainly with administration of steroids followed by application of nonsteroid products, such as, in psoriasis, anthralin, coal tar, and calcipotriol.

Psychophysiology of stress in dermatology. The psychobiologic pattern of psychosomatics.

Stress is an abnormal or extreme adjustment in the physiology of an animal to cope with adverse effects of its environment and management. The adverse effect is designated the stressor. In this article, the authors try to focus on the main types of host factors that can influence stress (genetics, perception) and on the numerous types of stressors (environmental, behavioral, psychological). Moreover, the authors outline the relevance of psychosomatic medicine, proposing the examination of psyche and soma as a unit "in sickness and in health." They focus their attention on the new aspects of biologic psychosomatics (psychoneuroendocrinimmunology) in dermatology, suggesting the possible role of neuropeptides in the pathogenesis of some common dermatoses such as psoriasis, atopic dermatitis, alopecia areata, and urticaria.

Therapeutic experience with ketoconazole.

The efficacy of ketoconazole was evaluated in forty-five patients with dermatophytoses, in twelve with candidosis, in two with fixed cutaneous sporotrichosis, in one with primary cutaneous cryptococcosis and in one with pulmonary aspergillosis. Patients received 200 mg daily of ketoconazole until complete cure, except for patients with vulvovagnitis who received 400 mg daily for five days. All patients with dermatophytoses were cured within 20 to 40 days. No recurrences were observed at post-therapy follow-up. Patients with candidosis were also cured, with only one recurrence. Patients with deep mycoses recovered, except for one with fixed cutaneous sporotrichosis, who showed slight improvement. No significant side-effects were observed during therapy. In conclusion, ketoconazole is an effective therapeutic agent for fungal infections.

Stress, stigmatization and psychosomatic purpuras.

Stress is a term that is readily recognized by everyone but defines rigorous scientific definition. It is widely interpreted as the emotional and biologic responses to novel or threatening situations. In humans, however, the term "distress" seems to be preferable, more clearly defining the fact that is the response that is being referred to, rather than the stimulus. Distress has been postulated to be capable of precipitating an overt illness, as when it occurs coincidentally with an incipient infection or neoplasm. Moreover, it is able to provoke several disorders and symptoms in many tissues and organs, including the skin. In this paper the authors focus on the main characteristics of stress and emphasize the relevance of psychosomatic medicine that proposes the simultaneous examination of psyche and soma. Special consideration is given to a peculiar form of skin disease, psychogenic purpura, together with the stigmata of mystics that, in large part, seem to be conditioned or provoked (or provocable) by emotional stress or by psychic influences on cutaneous fibrinolytic activity.

The effect of thymopentin treatment on the relapse rate in frequently relapsing herpes simplex virus infections.

Twenty-four patients suffering from longstanding severe recurrent herpes simplex, who had not responded to prior therapy, were treated with s.c. thymopentin injections 50 mg, three times weekly, over a period of six weeks. They were followed up at weekly intervals over this period and then six weeks later. Moreover, the longest relapse-free period observed in the year after the treatment was recorded in the investigator's documentation. Thirteen of the 14 patients with labial herpes simplex and 10 of the 13 patients with genital herpes simplex improved markedly as shown by a decrease in the relapse rate of at least 50%, shorter episodes of relapse and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than four months after cessation of the therapy. No serious side-effects were observed. Laboratory examinations before, during and after thymopentin did not reveal significant alterations except for an increase in the T-helper/T-suppressor ratio. The effect of thymopentin is assumed to be due to T-helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon.

The biosynthesis of prostaglandins in psoriatic skin.

The biosynthesis of prostaglandins (PGs) was studied in biopsy material taken from 8 psoriatics and 7 healthy controls. The psoriatic skin showed a statistically significant reduction in the capacity for PG synthesis: in psoriatic skin PGE2 was 301 +/- 74 ng/g wet weight and PGF2 alpha 425 +/- 89 ng/g wet weight, whereas in healthy skin the synthesizing capacity of PGE2 was 507 +/- 45 ng/g wet weight and of PGF2 alpha 730 +/- 206 ng/g wet weight.

Plasminogen activation in psoriasis.

Plasminogen activation is a widely documented physiological phenomenon in which plasminogen activators (mainly urokinase and tissue type plasminogen activator) transform the zymogen plasminogen into the wide-spectrum proteinase plasmin. We show here that psoriatic epidermis is provided with abnormal plasminogen activator activity, mainly dependent on the activity of tissue type plasminogen activator and that this abnormal activity can be reversed with common topical treatments (i.e. anthralin, and 0.1% betamethasone valerate cream). We also report abnormal immunohistochemical localization of plasminogen, urokinase and tissue type plasminogen activator in psoriatic epidermis which returned to normal after the topical treatments. These data suggest a major role of plasminogen activation in the pathogenesis of psoriasis.

[Evaluation of cell-mediated immunity in the course of primary malignant tumors of the ovary. Cutaneous reactivity. (author's transl)]. / Valutazione della immunità mediata da cellule in corso di tumori maligni primitivi dell'ovaio. La reattività cutanea

The present possibilities of clinically evaluating cell-mediated immune potential using skin reactivity to microbial protein antigens (streptokinase-streptodornase; tuberculin; formalin-killed parotitis virus) together with a contact sensitized such as dinitrochlorobenzene are examined. A single evaluation index for the set of cutireactions is proposed and, as a practical example, the delayed hypersensitivity data based on intradermal and patch tests in 41 cases of primary malignant tumor of the ovary are reported. There is a definite correlation between immune impairment and cancer spread, with a survival prognosis value even in initial cases.