[Kidney transplants in Sicily. Our experience with surgery and CyA immunosuppression].
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Biomedical subjects
Publications and source records attributed to A Palermo.
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Continuing controversy exists concerning a possible relation between neoplastic cells of malignant fibrous histiocytoma (MFH) and the mononuclear phagocyte system. The aim of this study was to investigate the membrane and cytoenzymatic phenotype of a primary cutaneous MFH, storiform pleomorphic type, and to compare these data with ultrastructural observations. Cytoplasmic proteins (acid phosphatase, non specific esterase, alpha-1 antitrypsin, and lysozyme) suggestive of a mononuclear phagocyte origin were demonstrated in varying amounts in neoplastic cells infiltrating the dermis. Consistent with these data, two (LeuM3 and OKM5) out of four (OKM1 and LeuM1) monoclonal antibodies directed against mononuclear phagocyte antigens stained most of the neoplastic cells. Class II MCH antigens (DR and DQ) were variably expressed on distinct groups of neoplastic cells, suggesting different activation/differentiation states. The results favor the view that the present case of primary cutaneous MFH was of mononuclear phagocyte origin. However, the observed phenotypic profile was expressed on neoplastic cells irrespective of their ultrastructural morphology (histiocytic or fibroblastic). Together with previous data in the literature, the latter finding corroborates the view that distinction between these two cell types in MFH is likely to reflect divergent growth and differentiation patterns rather than histogenesis.
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The leukemic cells circulating in the peripheral blood and invading the skin of a patient with type M5 myelomonocytic leukemia were compared using ultrastructural, cytochemical and immunological criteria. Neoplastic cells exhibited more differentiated morphologic features in the skin than in peripheral blood, resembling tissue macrophages. The cytochemical pattern did not show any appreciable difference, whereas the surface antigenic profile was dissimilar. Most circulating leukemic cells were Leu M1+ and Leu M3+, and the percentage of OKM1+ and OKIa-1+ cells varied in two different blood samples examined. Conversely, OKIa-1 monoclonal antibody stained virtually all the leukemic cells infiltrating the skin in the absence of any appreciable reactivity with the other monoclonal antibodies. The phenotype of the malignant cells in the skin did not vary during the clinical course of the disease. These observations suggest that the cutaneous microenvironment is able to induce leukemic cells to mutate their phenotypic features towards a more mature state, or that only relatively differentiated circulating leukemic cells are able to leave the bloodstream and colonize the skin.
Ketanserin (K), a selective and specific S2-receptor antagonist, has been compared with metoprolol (M), a cardioselective beta-blocker, in a double-blind study in order to assess its efficacy and safety in the treatment of essential hypertension. After a placebo run-in period of 4 weeks, hypertensive patients [supine diastolic blood pressure (DBP) greater than or equal to 100 mmHg] were treated with K, 40 mg twice daily (n = 18), or with M, 100 mg twice daily (n = 14). Systolic pressure (SBP) and DBP, both supine and standing, were significantly reduced from the first month of treatment by both drugs and remained stable for the whole study period (12 weeks). About two-thirds of the patients treated with K responded to the therapy (drop in DBP of at least 10%) and half were normalized (DBP less than or equal to 90 mmHg). In the M group, 50% of patients responded and 30% were normalized. A significant decrease in the heart rate was observed with M, but not with K. Ten patients treated with K were followed for 1 year. The antihypertensive effect of K was maintained throughout the study with evidence of tolerance. No serious adverse reaction was observed.
As a source of peripherally available vasoactive agents, platelets may play a role in many cardiovascular events. This study aimed to assess the functional role of serotonin released by platelets in mediating the effects of sympathetic stimulation on vascular tone in healthy subjects. Platelet serotonin (5-HT) content and plasma catecholamine concentrations were measured by high performance liquid chromatography with electrochemical detection in blood samples drawn from 10 healthy subjects undergoing tilt test, cold pressor test, treadmill and isometric exercise by handgrip. It was possible to identify both responder subjects who showed a significant decrease in 5-HT platelet content and non-responder subjects who showed no significant change. Stress-induced increases in plasma catecholamine levels were higher in the responders. This suggests that some subjects were more susceptible to adrenergic stimuli and that the elevated concentrations of circulating catecholamines may induce platelet activation and 5-HT release. Analysis of the cardiovascular responses to the tests suggests that 5-HT released by platelets upon adrenergic stimulation in healthy subjects might induce a vasodilatory response modulating sympathetic tone.
To assess whether and how the activation of the renin-angiotensin system that occurs in response to changes in posture contributes to the maintenance of blood pressure, we measured blood pressure, heart rate, plasma noradrenaline and plasma active and inactive renin in patients with essential hypertension in the supine, sitting and standing positions, (each sustained for 30 min), before and after administration of captopril. These studies were performed before and after a brief period of diuretic therapy. Both in the normal and in the sodium depleted state captopril reduced the normal adaptive response of blood pressure to changes in body position, whereas the responses of heart rate and plasma noradrenaline to these stimuli were unaffected by captopril. In contrast, the postural increases in active renin were magnified after captopril while inactive renin was unchanged throughout these acute studies. Our results indicate that during mild but rather prolonged postural stresses the generation of angiotensin by active renin supports blood pressure either through its direct vasoconstrictive effect and/or by potentiating the activity of the sympathetic nervous system. It is unlikely that the changes in active renin depend upon conversion from the inactive form.
The phenotypic profile of atypical cells from a patient with cutaneous multilobated T-cell lymphoma was investigated using a multiparameter approach including evaluation of membrane markers, cytochemistry, and functional activity. Retroviral sequence restriction analysis was also used to investigate the presence of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in atypical cells infiltrating the skin and in otherwise normal peripheral blood lymphocytes. The atypical cells appeared to belong to the T-lineage demonstrating OKT11 positivity, E-rosette formation, tartrate-sensitive acid phosphatase and beta-glucuronidase activity, and consistent negativity for cytoplasmic and/or surface monoclonal immunoglobulins. However, they failed to stain for other T-lymphocyte-associated antigens, such as those defined by OKT3, OKT4, OKT6, OKT8, OKT9, OKT10, Leu-2a and Leu-3a monoclonal antibodies, and did not express a definite alpha-naphthyl-acetate esterase pattern. Additional studies including phagocytosis tests and a series of monoclonal antibodies against phagocytic and natural killer cell associated antigens were all negative. No HTLV-I related sequences were found in either the cells infiltrating the skin or in circulating lymphocytes. To our knowledge, in previously reported cases of cutaneous multilobated cell lymphoma a clear T-lymphocyte phenotypic profile was demonstrated. Our present data indicate that this is not always necessarily the case. The peculiar phenotype we found might represent a transitional state between different T-cell subsets or an as yet unrecognized phenotype of a neoplastic T-lymphocyte which lacks a normal counterpart.
This paper reports the results of a series of light and electron microscopic, cytochemical, immunologic and cytogenetic investigations performed in a patient with Sézary syndrome. Fifty-two percent of the cerebriform cells were OKIa-1 positive and 55% were acid alpha-naphthyl-acetate esterase (ANAE) negative. Since activated T-lymphocytes are known to lose their peculiar ANAE activity while acquiring Ia-like antigens, it is conceivable that the ANAE-negative and OKIa-1-positive cells represent an in vivo activated subset. Thus, it appears that a typical Sézary cell population from a given individual can exhibit heterogeneous phenotypic profiles.
A 61-year-old female with a well-established Mycosis fungoides also had a marked hypereosinophilia, a monoclonal gammopathy IgGk type, and an elevated IgE level. Such unusual association of abnormalities of the immune system in a given Mycosis fungoides patient has not been described before in the absence of any other underlying cause.
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Prazosin, a selective antagonist of postsynaptic alpha-adrenoreceptors, was used to investigate the influence mediated by the juxtaglomerular alpha-adrenoreceptors on renin release in man. We studied, in seven patients with essential hypertension, the acute effects of 0.25 mg prazosin, given intravenously, on blood pressure and plasma renin activity, the degree of alpha-blockade induced by the drug being assessed by comparing the increments in blood pressure following a test dose of phenylephrine before and after prazosin administration. We also measured the increments in plasma renin activity in response to beta-adrenergic stimulus consisting of an isoproterenol challenge, before and during the prazosin induced alpha blockade. Prazosin infusion caused, within 20 min, a marked reduction of the pressor response to phenylephrine, a significant increment in plasma renin activity, and no change in blood pressure. The increments in renin in response to isoproterenol were significantly greater, both in absolute and percent values, after rather than before prazosin. These results indicate that the increase in renin during systemic alpha 1-adrenoreceptor blockade may be independent of the fall in blood pressure and support the view that the juxtaglomerular alpha 1-adrenoreceptors participate in the regulation of renin release with an inhibitory action, which antagonizes the stimulating influence of the beta-adrenoreceptors.
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