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Biomedical subjects

A F Finzi

Publications and source records attributed to A F Finzi.

At least 37 records · Page 2Linked to original sources

Intramuscular low dose alpha-2B interferon and etretinate for treatment of mycosis fungoides.

BACKGROUND: Mycosis fungoides is a lymphoma of cutaneous origin characterized by a proliferation of cells with a T phenotype. METHODS: In this pilot study, 13 men with mycosis fungoides in various stages were treated with alpha-2b interferon and etretinate. RESULTS: In ten of them, such a therapy proved to be effective (7 complete responses, 3 partial responses), sometimes with prolonged remissions (up to 20 months, and still persistent) after suspension of the drugs. CONCLUSIONS: We chose low-dose interferon administration in order to prevent side effects, which are said to be dose-dependent. In our experience this is not true, but this drawback seems to be overcome by the very good, sometimes spectacular, response to this combination therapy, particularly in low stage forms of the disease. This fact, compared with results provided by other groups, prompts us to plan new research protocols based on associations of retinoids with different interferon types (or even associations of different interferons), because we believe they will have an important place in treatment of cutaneous T-cell lymphoma in future.

Adult↗

Cyclosporin in psoriasis: pathophysiology and experimental data.

Cyclosporin has been used efficaciously in recent years for the management of severe psoriasis. The remarkable efficacy of this drug and its known immunosuppressive properties have indicated even more strongly the involvement of the immune system in the induction and maintenance of psoriasis. The present review summarizes the role of cellular immunity in the pathogenesis of psoriasis and possible mechanisms of action of cyclosporin in psoriasis, and describes the laboratory studies performed in our Department under two headings, changes in lesional immune infiltrate (evaluated immunohistologically) and changes in neutrophil chemotaxis during cyclosporin treatment. Our immunohistological study showed that the psoriatic plaques contained an infiltrate composed mainly of activated CD4+ T cells. Cyclosporin treatment significantly decreased T cells and normalized the distribution and antigen expression of intraepidermal Langerhans cells, increasing the number of CD1+ dendritic cells. Our studies on neutrophil chemotaxis showed that cyclosporin reduced the chemotactic activity of neutrophilic polymorphonuclear leukocytes (in vivo but not in vitro), seemingly as a consequence of blocking the production of chemoattracting cytokines by psoriatic monocytes.

CD4-Positive T-Lymphocytes↗

[Erosive lichen planus of the glans penis. Treatment with cyclosporin A].

After suffering from chronic and steroid-resistant erosive lichen planus of the glans penis for 2 years, a 42-year-old patient presented to our Institute. The clinical picture was of an erythematous and erosive lesion, superficially covered with sero-fibrinous exudations. Lichen planus was diagnosed by clinical and histological examination. Control routine serum analysis and urinalysis gave normal results, and ciclosporin A was given at a dosage of 3 mg/kg daily. After 2 weeks of therapy, significant regression of erythema and infiltration was seen, so that the patient could be circumcised as planned. After leaving our Institute the patient continued the therapy with ciclosporin A and the monthly controls of kidney and liver function had shown no abnormalities during the 6-month follow-up that had elapsed up to the time of writing.

Adult↗

Plasma alpha-melanocyte-stimulating hormone, beta-endorphin, met-enkephalin, and natural killer cell activity in vitiligo.

BACKGROUND: The immune system is important in the pathogenesis of vitiligo, and emotional stress has precipitated vitiligo in some patients. Opioid peptides, beta-endorphin, met-enkephalin, and alpha-melanocyte-stimulating hormone (MSH) act as immunomodulators, and their secretion increases during periods of stress. OBJECTIVE: To see whether these three neuropeptides might be related to vitiligo itself or to some alterations of the immune system in patients with vitiligo, we compared circadian variations in their plasma concentrations and natural killer cell activity of peripheral blood lymphocytes in 14 patients with vitiligo with those of 12 healthy subjects. METHODS: Plasma concentrations of neurohormones were evaluated by radioimmunoassay (immunoradiometric assay for beta-endorphin). Natural killer cell activity (NKCA) was assayed against K562 cells by 51Cr release technique. Data were compared by the Student t test and analyzed by cosinor analysis. RESULTS: The NKCA in vitiligo patients was higher than in controls but had similar circadian rhythm. alpha-MSH had no circadian rhythm in controls or in patients; plasma alpha-MSH levels were the same. Daily met-enkephalin and beta-endorphin oscillations in patients were no longer circadian. beta-Endorphin plasma levels in stable vitiligo were higher than in controls. There were no differences between patients with active vitiligo and normal subjects. Met-enkephalin plasma levels were generally higher in vitiligo patients, especially in the one with active vitiligo, than in controls. CONCLUSION: In vitiligo there are aberrations in neuropeptide, beta-endorphin, and met-enkephalin secretion. The plasma met-enkephalin level is positively correlated with the aggressiveness of the disease.

Adult↗

Immunohistologic evaluation of the effect of cyclosporine treatment on the lichen planus immune infiltrate.

We have investigated immunohistologically the cutaneous immune infiltrate in the lesions of five patients with severe, extensive lichen planus of recent onset before and after 15 days of oral, low-dose cyclosporine therapy (3 mg/kg/day). Before therapy, we observed an abnormal bandlike cellular infiltrate localized in the papillary dermis, composed mostly of CD3+ cells, with a prevalence of CD4+ cells. Infiltrating lymphocytes showed markers of activation (HLA-DR antigens and interleukin 2 receptor), and there were many Langerhans (CD1+) cells in the dermal infiltrate. After 15 days of cyclosporine therapy, we observed a dramatic decrease in the total number of T cells and a corresponding decrease in interleukin 2 receptor-positive activated CD25+ cells and in antigen-presenting cells (CD1+ and CD14b+). These changes were concurrent with clinical improvement. Our results are compatible with the hypothesis that the inhibition of CD4 T cells by cyclosporine might explain the drug's therapeutic action and that the interaction between antigen-presenting cells and CD4 T cells is important in the pathogenesis of lichen planus.

Adult↗

Association between circadian rhythms of endogenous hypothalamic opioid peptides and of natural killer cell activity.

To explore in man the hypothesis that natural killer cell activity and hypothalamic-hypophyseal hormones constitute a mutually coupled multioscillatory system, we analysed and compared, in 11 healthy volunteers, the circadian variations in plasma concentrations of beta-endorphin, met-enkephalin and alpha-MSH, and of natural killer activity of peripheral blood lymphocytes. Natural killer cell activity and plasma beta-endorphin levels showed a similar circadian rhythm with the peak in the morning (acrophases at 06.14 and 08.25, respectively), whereas the circadian rhythm of met-enkephalin was approximately in antiphase to the natural killer rhythm (acrophase close to 17,00 hours). Although daily variation of alpha-MSH showed greater inter-individual variability, a circadian rhythm was statistically validated. Analysis of correlation between rhythmometric parameters (mesor, amplitude, peak and nadir) of natural killer cell activity vs neuro-endocrine hormones revealed that the minimum and medium daily concentrations of beta-endorphin correlated directly with the corresponding parameters of natural killer activity, while the maximum and medium concentrations of met-enkephalin were inversely correlated with the peak and the mesor of natural killer activity. The amplitude of natural killer cell activity oscillations correlated directly with the peak, mesor and nadir concentrations of alpha-MSH. We show here that circadian rhythms of some neuroendocrine hormones of the hypothalamic-hypophyseal axis, i.e. beta-endorphin, met-enkephalin and alpha-MSH, are significantly coupled to daily oscillations of NK cell activity.

Adolescent↗

Psoriatic arthritis.

Explore the source record for details and available documents.

Arthritis, Psoriatic↗

Immunohistological evaluation of basal cell carcinoma immunoinfiltrate during intralesional treatment with alpha 2-interferon.

We investigated the peritumoral and intratumoral immune infiltrate in 6 basal cell carcinomas (BCCs) treated with recombinant alpha 2b-interferon. Each BCC was injected intralesionally three times a week for 3 weeks with 1.5 x 10(6) IU of interferon per injection (total dose 13.5 x 10(6) IU). The immunohistological study was done before the start of interferon therapy and 15 days afterwards, using a series of monoclonal antibodies and an immunocytochemical technique. Before therapy the infiltrate consisted mainly of CD3+ (T) cells, with prevalence of CD4+ (helper/inducer) T cells. The percentage of T cells expressing interleukin-2 receptor (CD25+ cells) was higher in the tumor nests than in the peritumoral infiltrate (20% and 11% respectively). CD1+ (Langerhans) cells and CD14b+ cells (monocytes/macrophages) were present in the peritumoral infiltrate in all cases (9% +/- 5% and 14% +/- 7% respectively). Very few CD56+ (natural killer), CD15+ (granulocytes) and CD20+ (B) cells were observed in the peritumoral infiltrate and none at all in tumor nests. After 15 days of interferon therapy, we observed an increase in peritumoral and intratumoral CD4+ cells. There was a decrease in the number of CD25+ cells and of CD1+ cells in the peritumoral infiltrate. The number of intratumoral CD25+ increased. No variations were seen in CD14b, CD15, CD20, and CD56 positive cells. Eight weeks after completion of therapy, two BCCs were cleared and the remaining four showed clinical and histological improvement. These results may indicate a direct effect of interferon against BCC; in addition the immunohistological findings suggest that intralesional interferon enhances T cell mediated immune response, especially in tumor nests.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

T cell subpopulations in vitiligo: a chronobiologic study.

The circadian rhythms of helper (CD4) and suppressor (CD8) T cells from the peripheral blood of 12 vitiligo patients (seven with active disease, five with static) and 12 healthy control subjects were studied. Patients with active vitiligo had a lower percentage of CD4+ cells than did control subjects at 0000 hours and at 0600 and 1200 hours; there were no differences between these values in patients with static vitiligo and those in control subjects. The percentage of CD8+ cells were lower at 1200 and 1800 hours in both active and static vitiligo patients than in control subjects. Cosinor analysis of the CD4+ cells showed a circadian rhythm in static vitiligo, whereas the rhythmicity was lost in active vitiligo. CD8+ cells did not show any circadian rhythm in either active or static vitiligo. Our data show more striking aberrations for T cell subtypes in active vitiligo than in static vitiligo. They suggest that cell-mediated immunity may play a role in the pathogenesis of the disease.

Adolescent↗

Factors secreted by untreated psoriatic monocytes enhance neutrophil functions.

Monocytes stimulated with bacterial lipopolysaccharides (LPS) release mediators that induce increased responses of human granulocytes. Recently we showed that psoriatic monocytes can stimulate neutrophil chemotaxis, phagocytosis, and O2- production without addition of LPS and this effect is inhibited by cyclosporin A. We have now investigated the presence of cytokines in supernatants from cultures of psoriatic monocytes (resting monocytes). These cells were cultured for 24 h in endotoxin-free medium. Normal human neutrophils were then incubated for 1 h with the resulting supernatants (sMS, or conditioned media). The sMS from unstimulated psoriatic monocytes significantly enhanced neutrophil chemotaxis and superoxide anion production. The enhancing factors are protein in nature and require ongoing protein synthesis, demonstrated by the facts that the activity in conditioned medium is labile to heat denaturation at 100 degrees C for 10 min, is not produced by monocytes cultured in the presence of puromycin, and is proteinase sensitive. Additional evidence suggested that extremes of pH inhibit activity. None of the conditioned media treated in these ways activated neutrophils. The neutrophil function-enhancing factors derived from psoriatic monocytes are in part cytokines, including TNF and GM-CSF. The support for this conclusion is the higher level of TNF and GM-CSF in media conditioned by psoriatic monocytes than in media conditioned by normal human monocytes, the inhibition of TNF production and neutrophil stimulating activity by cyclosporin A, and the inhibition of neutrophil stimulating activity in conditioned media preincubated with anti-TNF and anti-GM-CSF antibodies. It is concluded that psoriatic monocytes spontaneously produce higher than normal levels of TNF alpha, GM-CSF, and, perhaps, other cytokines that might be responsible for the enhanced activity of psoriatic neutrophils.

Cell Survival↗

HLA-A, B, C and DR antigens in nickel contact sensitivity.

The relationship between HLA antigens (A, B, C and DR) and nickel contact sensitivity was examined in 54 patients with contact allergy, as confirmed by an unequivocal positive patch-test reaction only to nickel. A control group was 320 healthy blood donors from the same geographical area as the patients. The HLA-A, B, C and DR antigens were typed using standard serological methods. HLA typing revealed a significant increase of HLA-DRw6 antigen in the patient group (corrected P less than 0.025) and the relative risk for patients with DRw6 to develop nickel sensitivity was 3.32.

Adolescent↗

Nimodipine versus terfenadine in the treatment of physical stimulus-induced urticaria.

Basophil and mastocyte degranulation is calcium-dependent. Calcium-antagonists can inhibit synthesis of and release in vitro some mediators in various types of cells. Both immunologically stimulated and non-immunologically stimulated release of material from basophils isolated from normal and allergic subjects can be antagonized by calcium blockers. The present study was aimed at testing the therapeutic effects and side effects of nimodipine therapy, a new dihydropyridine anti-calcium derivative for physical stimulus-induced urticaria, in comparison with a standard H1-antihistamine therapy. The study was done in 32 outpatients who had physical stimulus-induced urticaria: 20 patients received nimodipine three times a day in a daily dose of 180 mg, 12 patients were treated with terfenadine in a dose of 120 mg. In the majority of patients treated with both nimodipine and terfenadine, satisfactory clinical results were obtained after 3 weeks of therapy. There were, however significant (P less than 0.05) differences in responses. Complete clearance after 3 weeks was noted in 50% patients treated with nimodipine, whereas only 16% of patients on terfenadine were completely clear, and some showed only slight improvement. The treatment was easily manageable, and with few side effects.

Benzhydryl Compounds↗

[Laser flow cytofluorimetry in the study of papilloma virus-induced lesions].

HPV insertion into the genome can cause permanent changes in cellular DNA that disturb the regulation of cell proliferation. Most HPV-induced epithelial proliferative disease are benign, but not all. We have studied both types of lesion by automated laser flow cytometry to see if there were any permanent changes in the DNA that might serve as reliable prognostic indicators. There were 101 lesions of interest to the dermatologist, stomatologist and gynecologist. Although fluctuations in yields of cells make it difficult to formulate definite conclusions, since many results are heterogeneous and hard to summarize, we found dysplastic and metaplastic lesions always to be hyper- or hypodiploid and to our surprise two cases of common wart were hyperdisploid and another hypodiploid. This present study shows that laser flow cytometry can detect changes in the genome of lesions known to become malignant when the histological degree of transformation still indicates only a preneoplastic condition. This raises the problem of how we should label lesions like common warts, since laser flow cytometry clearly shows that they have net changes, though slight, in DNA content.

Biopsy↗

Circadian rhythm of natural killer cell activity in vitiligo.

Ten patients with vitiligo, either in the active (six cases) or static (four cases) phase, and twelve healthy control subjects were studied with a standard cytotoxicity assay to evaluate the circadian rhythm of natural killer cell activity from peripheral blood mononuclear cells. The natural killer cell activity was measured at the zero, sixth, twelfth, and eighteenth hours of the day. The results demonstrated that patients with vitiligo had significantly higher natural killer cell activity compared with normal controls. When patients with static and active vitiligo were compared, those with the static form had increased natural killer cell activity at all times except noon, whereas those with active form had increased natural killer cell activity only at 0600 and 1800. These changes shifted the acrophase of the circadian rhythm of each group. Indeed, by cosinor analysis, both patients with vitiligo and normal controls had similar circadian rhythms, but the acrophase was shifted from 0602 in control subjects to 0435 in the ten patients with vitiligo. The acrophase in the six patients with active vitiligo was found to be closest to that of normal controls (0508). These findings indicate that natural killer cell activity abnormalities are more marked in the static rather than in the active form of vitiligo.

Adult↗