[Some clinical symptoms and allergens on asthma-prurigo syndrome]. / Niektóre objawy kliniczne oraz alergeny w zespole asthma-prurigo.

The group of 146 patients suffering from asthma-prurigo syndrome (85 adults and 64 children) have been inquired in many various clinical centers. It was established that in 79.6% of the patients the first symptoms of illness appeared already in infancy and only 28.2% of the patients had negative familiar anamnesis on the allergy. In 73.2% of the patients with asthma-prurigo syndrome the symptoms of atopic dermatitis persisted longer than asthma symptoms and in 89.9% of them asthma-prurigo symptoms accompanied other form of allergic diseases. The most important causal allergens provoking asthma-prurigo symptoms were: house dust (in 64.4% of the patients), chocolate (in 42.2%), cat epithelia (in 40.2%) and cow milk proteins (in 29.5% of the patients).

[Changeability of respiratory tract and skin symptoms in patients with asthma-prurigo syndrome under the influence of emotional and environmental factors]. / Zmiennosc nasilenia objawów ze strony dróg oddechowych i skóry u chorych z zespolem asthma-prurigo pod wplywem czynników emocjonalnych i srodowiskowych.

In a group of 228 patients suffering from asthma-prurigo syndrome the influence of emotional state, permanent residence and season time on dynamic of the clinical symptoms were studied. The evaluation of emotional state in 80 adult patients was carried-out by means of Eysenck Personality Inventory. The emotional state had less negative influence on the exacerbation of the symptoms upon children then in adults (especially on their skin symptoms). It was confirmed that the patients with high level of neurotic symptoms revealed easier the exacerbation of asthma and skin disorders under the influence of emotional stress. The climatic treatment on the sea-side was more efficient for them than any mountain climatic cure, especially in the treatment of airways symptoms. Similarly, the summer season brought the relief of their symptoms from both the respiratory and skin symptoms.

Interleukin-12 inhibits angiogenesis induced by human tumor cell lines in vivo.

Tumor cell-induced angiogenesis, i.e., new blood vessel formation within tumor tissue, is an essential requirement for the growth of solid neoplasms. Interleukin-12 (IL-12) inhibits growth of a variety of experimental tumors in vivo. We tested whether antitumor activity of IL-12 is related to the inhibition of angiogenesis induced by tumor cell lines. Angiogenesis was induced in x-ray immunosuppressed Balb/c mice by intradermal injection of the following human tumor cells: T47D, originating from mammary carcinoma; A431, derived from vulval carcinoma; and Skv, established from bowenoid papulosis, Systemic treatment of the mice with murine IL-12 significantly decreased angiogenesis induced by human tumor cells in a time-and dose-dependent manner. Preincubation of human cells in vitro with IL-12 did not inhibit tumor cell-induced angiogenesis, suggesting that the antiangiogenic capacity of IL-12 is restricted to in vivo conditions. Treatment of the mice with rat antibody against murine interferon-gamma (IFN-gamma) resulted in counteracting the antiangiogenic effect of murine IL-12. Furthermore, human IFN-gamma inhibited the angiogenic activity of human tumor cell lines. This indicates that IFN-gamma is a mediator of the antiangiogenic effect of IL-12. The results show that the mechanism of antitumor action of IL-12 may depend not only on the immunostimulatory activity of this cytokine but also on its effect on tumor cell-induced angiogenesis. IL-12 should be considered as a potential candidate for the treatment of angiogenesis-dependent malignancies.

Vitamin D3 is a potent inhibitor of tumor cell-induced angiogenesis.

Vitamin D3 derivative 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) exerts various biological effects in cells that possess vitamin D3 receptor (VDR), including enhancement of cell differentiation and inhibition of cell proliferation. These activities of 1,25(OH)2D3 might be responsible for its anti-neoplastic effects, as shown in various experimental systems. The aim of this study was to compare the anti-angiogenic activity of 1,25(OH)2D3, retinoids, and interleukin-12 (IL-12) in an experimental tumor cell-induced angiogenesis assay in mice. Tumor cell-induced angiogenesis assay was performed in x-ray immunosuppressed BALB/c mice by intradermal injections of human tumor cell lines of different origin. The injections resulted within 3 d in a local formation of new blood vessels, and the intensity of angiogenesis correlated with the number of injected cells. Systemic treatment of the mouse recipients with 1,25(OH)2D3 significantly decreased angiogenesis, comparable to the effect of retinoids (all-trans retinoic acid [RA], 9-cis RA and 13-cis RA) and of IL-12. In vitro preincubation of the cells with all compounds (except IL-12) led to the inhibition of their angiogenic capability in vivo. Moreover, combination of 1,25(OH)2D3 and retinoids resulted in a synergistic inhibition of angiogenesis. The results strongly suggest that anti-angiogenic compounds with relatively low toxicity (e.g., 1,25(OH)2D3, retinoids, and IL-12) and their combinations could be beneficial in the treatment of some angiogenesis-associated malignancies.

Retinoids, interferon alpha, 1,25-dihydroxyvitamin D3 and their combination inhibit angiogenesis induced by non-HPV-harboring tumor cell lines. RAR alpha mediates the antiangiogenic effect of retinoids.

Retinoids combined with interferon alpha-2a (IFN alpha) or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] have shown marked synergistic inhibitory effects on angiogenesis induced by tumor cell lines harboring DNA of oncogenic human papillomaviruses (HPV) type 16 or 18. This report demonstrates comparable effects of these compounds on angiogenesis induced by non-HPV-bearing transformed cell lines, including breast carcinoma (T47D) and vulval carcinoma (A431) cell lines. Systemic treatment of mice with all-trans retinoic acid, 13-cis retinoic acid, 9-cis retinoic acid, IFN alpha or 1,25(OH)2D3 significantly decreased tumor cell-induced angiogenesis (TIA). In vitro pretreatment of T47D and A431 cells with these compounds also led to inhibition of their angiogenic capability when tested in the TIA assay. The inhibitory effects of retinoids could be counteracted by a selective antagonist of the nuclear retinoic acid receptor RAR alpha, suggesting a RAR alpha mediated mechanism of angiogenesis inhibition. The antiangiogenic effect of retinoids could be significantly enhanced by combination with IFN alpha or 1,25(OH)2D3. The results provide a further basis for the use of combinations of retinoids with IFN alpha or 1,25(OH)2D3 in the treatment of angiogenesis-dependent malignancies.

Synergistic effect of retinoids and interferon alpha on tumor-induced angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines.

Various retinoids and interferons exert anti-tumor effects both in experimental studies and in clinical trials. Recent reports indicate that they have a synergistic antineoplastic activity. Our study aimed to determine whether these synergistic anti-tumor effects are related to inhibition of tumor-cell-induced angiogenesis. A further aim was to compare the anti-angiogenic activity of various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic acid receptor RXR, given alone and in combination with interferon alpha-2a (IFN alpha-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse was used. Angiogenesis was induced by intradermal injection of HPV16- or HPV18 DNA-harboring tumor-cell lines. All-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as IFN alpha-2a applied to mice intraperitoneally for 5 consecutive days before induction of angiogenesis resulted in significant inhibition of angiogenesis. Combination of retinoids with IFN alpha-2a led to a synergistic inhibition of angiogenesis, as compared to the effects of the drugs given alone. Similar results were obtained when tumor cells were preincubated in vitro with the compounds, before injection into untreated mice. Our findings on synergistic anti-angiogenic effects of retinoids and IFN alpha-2a could explain, at least partially, the anti-tumor efficacy of combined therapy with these agents, and provide support for the role of angiogenesis in tumor growth.

Frequency and significance of the major and minor features of Hanifin and Rajka among patients with atopic dermatitis.

In 481 patients with atopic dermatitis (AD), 4 major features of Hanifin and Rajka were found in 72%, and in 96% over 6 minor features were seen, which is much more than the minimum required by these authors for making a 'firm diagnosis'. The incidence of particular minor features in all patients was varying significantly, and in subgroups of patients they appeared with different frequency. For example, asthma occurred more often in AD patients with the onset of skin lesions before the 6th month of life, and food intolerance was more frequently observed in patients with very high serum IgE level. In the control groups some minor features also occur but less frequently than in AD patients. We conclude that the anterior neck folds and Dennie-Morgan infraorbital fold should be regarded as minor AD features.

Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination.

Tumor-induced angiogenesis (TIA), i.e., the ability of transformed cells to stimulate new blood vessel formation is an important factor contributing to tumor growth and invasiveness. The antiangiogenic effect of the retinoids, all-trans retinoic acid, 13-cis retinoic and 9-cis retinoic acid, of 1,25-dihydroxyvitamin D3, and of their combinations were studied using an experimental system in vivo. TIA was induced in immunosuppressed mice by intradermal injection of the two human transformed keratinocyte lines, Skv-e2, harboring DNA of human papillomavirus (HPV) type 16, and HeLa, harboring HPV18 DNA. The three retinoids and 1,25-dihydroxyvitamin D3, when administered systemically to mice, before the angiogenesis assay significantly decreased TIA. Their combination led to a synergistic inhibition of TIA. These results provide the basis for the use of combination of retinoids and 1,25-dihydroxyvitamin D3 in treatment of neoplastic diseases.

Antitumor action of retinoids: inhibition of tumor cell line-induced angiogenesis and prevention of tumors in mice.

Acitretin was shown to inhibit angiogenic response to the tumorigenic SKV cell line bearing HPV16 genome and to sarcoma L-1 cell line, both in vitro and in vivo systems. The lowered angiogenic response to tumor cells was independent of duration and timing of the application of acitretin to animals. Acitretin, but not etretinate, was also found to be effective in the prevention of sarcoma tumors in mice.

Acitretin decreases tumor cell-induced angiogenesis.

The effects of acitretin and etretinate on angiogenesis induced in Balb/c mice by intradermal injection of keratinocyte tumor cell lines were evaluated. It was shown that both retinoids are capable of inhibiting angiogenesis evoked by a human epidermoid carcinoma cell line (A431). Acitretin, but not etretinate, inhibited also angiogenesis induced by the spontaneously transformed murine keratinocyte cell line Pam 212 and by the established tumorigenic SKv cell line harboring the HPV16 genome. We suggest that inhibition of blood vessel formation may be one of the mechanisms responsible for the anticancerogenic effect of retinoids.

Beta-carotene in prevention of cutaneous carcinogenesis.

Beta-carotene, administered orally to mice, caused a decrease in angiogenesis evoked by HPV-transformed tumorigenic cell lines (SKv-t, HeLa). It did not affect angiogenesis induced by the non-tumorigenic SKv (not-t) cell line, and increased lymphocyte-induced immune angiogenesis. We suggest that the anti-cancerogenic effect of beta-carotene may be due, at least in part, to its inhibitory effect on formation of new blood vessels within the tumour mass.

[Local use of leukotriene inhibitor--NDGA in psoriasis]. / Miejscowe stosowanie inhibitora leukotrienów--NDGA w luszczycy.

NDGA is known as an inhibitor of leukotrienes and may exert some effect on psoriatic lesion formation. The aim of the study was to test the influence of this drug on appearance of psoriatic plaques. 7 day application of 0.015% NDGA on psoriatic lesions under occlusion in 23 patients, gave some flattening of lesions as compared to controls. However, after finishing of application all the changes reappeared in previous form. We have never observed permanent beneficial effect in any patient.

[Treatment of head pediculosis. Comparative studies of a shampoo containing 0,33% Pyrethrum extract and shampoo containing 1% malathion]. / Leczenie wszawicy glowy. Badania porównawcze szamponu zawierajacego 0.33% wyciagu z chryzantem (pyretrum) i szamponu zawierajacego 1% malationu.

The insecticidal effect was tested of a shampoo with 0.33% of pyrethrum extract and a shampoo with 1% malathion. The study was carried out in 222 patients and better results were observed with the pyrethrum shampoo which required only one application.

Lymphocyte-induced angiogenesis assay--in cutaneous malignancies and cutaneous and genital warts.

Lymphocyte-induced angiogenesis assay (LIA) was used to evaluate immunocompetence of lymphocytes obtained from patients with basal cell carcinoma, squamous cell carcinoma, genital viral warts and from renal allograft patients under immunosuppressive therapy with multiple cutaneous warts. LIA revealed no abnormalities of angiogeneic capabilities of lymphocytes, except these from immunosuppressed patients which evoked significantly lower angiogeneic reaction than lymphocytes from healthy controls.

Modulatory effect of sera from scleroderma patients on lymphocyte-induced angiogenesis.

Sera from 22 patients with progressive systemic sclerosis were tested for the ability to modify the angiogenic capability of normal human mononuclear cells. The sera from patients with acrosclerosis, including the abortive form (CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), markedly enhanced this capability compared with sera from both healthy donors and patients with severe acrosclerosis and diffuse scleroderma. The enhancing effect of sera from patients with acrosclerosis decreased and/or disappeared in cases where the patient's acrosclerosis was chronic and severe. Thus, this test may be of diagnostic value in distinguishing various subgroups of systemic sclerosis.

Angiogenic capability of peripheral blood mononuclear cells in psoriasis.

The angiogenic capability of peripheral blood mononuclear cells (MNCs) from patients with psoriasis was tested by lymphocyte-induced angiogenesis assay. The study was performed in 36 patients with psoriasis vulgaris, six with generalized pustular psoriasis of the von Zumbusch type, and five with palmo-plantar pustular psoriasis. When patients with psoriasis vulgaris were considered as a whole, no significant differences in the angiogenic capability of their MNCs could be detected, as compared with controls. However, when cases of psoriasis were classified into various types, the differences in angiogenic capability of MNCs became evident. This capability was found to be markedly increased in the active form of psoriasis vulgaris and decreased in the stationary stage of the disease. It was increased in palmo-plantar pustular psoriasis but markedly decreased in generalized pustular psoriasis of the von Zumbusch type.

The adherence to human endothelium and plastic of neutrophils from psoriatic patients, and the effects of psoriatic patients' sera on normal neutrophils.

Circulating polymorphonuclear neutrophils (PMNs) from 50 patients with psoriasis vulgaris and from 38 control individuals (28 healthy blood donors and 10 patients with systemic sclerosis) were tested for their ability to adhere to human endothelial cell monolayer and a plastic surface. We also studied the effect of sera from psoriatic patients on the adherence and chemotactic activity of normal human neutrophils. The neutrophils from patients with psoriasis were much more adherent to the endothelium and the plastic surface, and this correlated positively with the activity of the disease, but inversely with the extent of the skin lesion. The sera from patients with active psoriasis were found to enhance the adherence and chemotaxis of normal human PMNs. Treatment of the sera by heat (56 degrees C for 30 min) did not affect their enhancing effect on the adherence but significantly decreased their effect on the chemotactic activity of normal PMNs.

Increased natural killer cell activity in patients with epidermodysplasia verruciformis.

Six patients with epidermodysplasia verruciformis (EV) were studied for natural killer cell (NKC) cytotoxic response of their peripheral blood mononuclear cells against K-562 target cells in an 18-hour chromium 51-release assay. Four patients displayed higher cytotoxic responses than controls did, whereas two others did not differ from controls. Patients with EV who had increased NKC activity were found to be infected with potentially oncogenic human papillomaviruses (types 5, 8, 9, 14, 17, 19, 22, 24, and others), and they have had multiple skin carcinomas and/or Bowen's precancerous dermatosis. Two patients with EV who had normal cytotoxic response were free of skin malignancies.

Inhibition of tumour-induced angiogenesis by systemically administered protamine sulphate.

Systemic administration of protamine sulphate significantly decreased the intensity of angiogenesis induced in X-ray immunosuppressed (BALB/c X DBA/2W) F1 mice by either HEp-2 (human larynx carcinoma) cells or semi-syngeneic splenocytes injected intradermally. In vitro experiments have shown that protamine sulphate markedly decreases the proliferation of human endothelial cells as assessed by 3H-TdR incorporation assay. In contrast, the proliferation of HEp-2 cells was not affected, and only slight inhibition of normal human fibroblasts could be demonstrated. Heparin abolished the inhibitory effect of protamine sulphate, both in vivo and in vitro. These results suggest that the observed inhibitory effect of protamine sulphate on angiogenesis in vivo may be at least partially due to the interaction of this compound with endothelial cells.

Decreased natural killer cell activity in generalized pustular psoriasis (von Zumbusch type).

Mononuclear cells isolated from the peripheral blood of four untreated patients with pustular psoriasis (von Zumbusch type) displayed greatly diminished natural killer cell activity against K-562 erythroleukaemic target cells in a 51Cr release assay when compared with mononuclear cells from healthy controls.