Myelodysplastic syndrome associated with increased bone marrow fibrosis and translocation (5;12)(q33;p12.3).
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Biomedical subjects
Publications and source records attributed to G Castello.
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Innovative approaches to cancer treatment have been made possible today by genetic engineering and hybridoma technologies. In this paper, attention is focused on the use of anti-idiotypic monoclonal antibodies such as internal tumor-associated antigens. These MoAbs may be able to overcome the immunosuppression in cancer patients by stimulating "silent" clones, or by allowing T cell help to become active, thus enhancing the overall immune response which the nominal antigen is unable to do. Preliminary experiences of active specific immunotherapy with monoclonal antiidiotypic antibodies in cancer patients are reported.
The activity of the membrane-bound and the purified erythrocyte Ca2+-ATPase in the absence of calmodulin was stimulated by calpain digestion but could be further increased to maximal levels by calmodulin (CaM). Thus, CaM sensitivity was retained by the digested ATPase, at least at short times of incubation. In membranes digested at higher temperatures and in the purified ATPase digested at higher calpain/ATPase ratios, the ATPase became fully activated. The membrane-bound and the purified 138-kDa ATPase were converted by calpain to a fragment of approximately 124 kDa which still bound CaM and could be isolated on CaM columns when proteolysis occurred slowly but not when it occurred rapidly. Carboxypeptidase digestion of the purified enzyme and of its fragment of about 124 kDa has shown that calpain attacked the CaM-binding domain near the C terminus of the ATPase. This has also been supported by digestion of the purified enzyme and of its fragment of about 124 kDa. A first cut occurred in the middle of the domain producing a fragment of about 14 kDa and a (CaM-binding) fragment of about 124 kDa. A second cut closer to the N terminus of the domain also produced a fragment of about 124 kDa and accounted for the loss of CaM binding at prolonged times of incubation of the ATPase with calpain.
We studied neopterin excretion levels and immunological features of 20 patients affected by Kaposi's sarcoma (KS), compared to 30 normal controls. Eighteen patients had the classic form of Kaposi's sarcoma (CKS), while two patients were anti-human immunodeficiency virus (HIV) seropositive and affected by the epidemic form associated with the acquired immunodeficiency syndrome (AIDS). In CKS patients, a trend of an increase of neopterin levels with more advanced stages appeared from our data whereas a significant reduction in CD3+ and CD4+ lymphocytes subsets was observed already at early stages (P less than 0.01). CD8+ cells did not show significant variations. A significant increase in serum IgA immunoglobulins (P less than 0.05) was also observed. Comparative analysis of the two patients affected by AIDS/KS showed the profound deficit in T-cell immunity but also the prognostic value of neopterin monitoring. Furthermore these findings seem to confirm Kaposi's sarcoma as an 'opportunistic neoplasia' and indicate neopterin as a useful prognostic marker.
Data reported in this paper emphasize the existence of close relationships between hepatitis delta patients and subjects affected by other viral diseases, first of all AIDS and related conditions. Some immunologic abnormalities characterizing initial stages of HIV infection (reduced CD4/CD8 ratio, based on increased CD8+ cells; B-cell polyclonal activation with the presence of circulating immune complexes) were found, in fact, also in delta patients. No statistically significant difference was observed by comparing delta vs no delta subjects.
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Male infertility may be due to a multiplicity of etiologic factors. In this study we have investigated the presence of cytomegalovirus (CMV) in 150 infertile men (selected after the exclusion of other etiopathogenic factors of infertility) and 80 subjects screened for pre-marriage consult. CMV was found in the sperm of 7/150 patients and 3/80 subjects screened for pre-marriage consult. Moreover, the seminal abnormalities evidenced in infertile men (a significant decrease of nemaspermic concentration and motility, of fructose, a significantly increased pH) were also observed in subjects screened for pre-marriage consult having CMV in the sperm. These abnormalities were related to alterations of cell-mediated immunity (decreased OKT4+, increased OKT8+ with decreased OKT4/OKT8 ratio). Among ten CMV+ subjects, two with idiopathic sterility and three subjects screened for pre-marriage consult showed a negativization of CMV in the sperm, during the observation period (one year), and a decreased anti-CMV titre lower than eight. Contemporary, a normalization of immunologic and seminal parameters was observed.
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Peripheral blood mononuclear cell populations in ten men, with idiopathic infertility with serum sperm agglutinating antibodies at a titre of 1/32, were evaluated. Mononuclear cells were enumerated using the monoclonal antibodies OKT3 (pan T cells), OKT4 (helper/inducer T cells), OKT8 (suppressor/cytotoxic T cells), Leu 7 (monocytes, null cells, and natural killer (NK) cells), OKIa (B cells, monocytes, null cells and activated T cells). Blood mononuclear cells with surface receptors for complement (B lymphocytes and a proportion of monocytes and null cells) were enumerated using a rosette test (EAC). The following abnormalities, compared to normal subjects, of blood mononuclear cell population were found: a decreased percentage of OKT3 (+) cells (p less than 0.01), a decreased percentage of OKT8 + cells (p less than 0.001) and increased OKT4/OKT8 ratio (p less than 0.001), an increased percentage of OKIAI cells (p less than 0.001). Levels of OKT4+ and Leu 7 cells and the percentage of EAC rosette forming cells were not significantly different from those in normal subjects. Regression analysis showed a significant correlation between the percentage of OKIAI cells and sperm agglutinating antibodies. After all that, significant correlation between humoral and cell-mediated immunity in patients with idiopathic infertility with antisperm autoantibodies, were observed.
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The cellular immune response of 58 patients affected by cervical cancer was evaluated with the aim of investigating abnormalities in T-cell populations. Subjects were divided into three groups: severe dysplasia or carcinoma in situ, microinvasive carcinoma, and invasive carcinoma. T cells were assessed by a spontaneous rosette formation test with sheep red blood cells and by reactivity with specific monoclonal antibodies of OKT series (OKT4 and OKT8 positive lymphocytes). A significant T-cell depression was observed in all patient groups; the lowest T-cell level was observed in group (b), which revealed an inverted OKT4+/OKT8+ ratio too. The results support the hypothesis that cell-mediated immunity is a key factor in premalignant status and in the early development of cervical cancer.
The authors evaluated the results of a study using clindamycin phosphate plus gentamicin in short-term therapy in patients with tumors submitted to surgery for removal of the primary lesion. Only 6.6% of these patients became infected, and these good results are most likely due to the synergic activity of clindamycin with the physiological immune response. This agent, in fact, was able to interfere with IgM/IgA immunoregulatory balance by enhancing IgM production and, consequently, phagocytic mechanisms.
Peripheral T-Lymphocyte subsets were analyzed with monolateral antibodies in 40 patients with Graves' ophthalmopathy. The 20 patients with untreated hyperthyroid exophthalmos showed a slight statistically not significant decrease in the percentage of total T-Lymphocytes and a statistically significant decrease with percentage of the OK T8 cells. No significant changes were observed in the percentage of OK T3 and OK T4 and OK T8 cells in patients with euthyroid exophthalmos under the drug treatment. These findings indicate the significant association of quantitative abnormality of suppressor-cytotoxic cells with untreated hyperthyroid exophthalmos.
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