A search for double minute chromosomes in cultured lymphocytes from different types of tumors.

Double minutes are considered the products of DNA amplification and are rare in normal human cells. They have been observed in cultured lymphocytes in selected samples of human populations as one of the characteristics of the so-called rogue cells. We scored 9500 metaphases of cultured lymphocytes from 65 subjects with a variety of heredity and sporadic tumors and from 30 healthy subjects. The 15 cells with double minutes were found in subjects with multiple endocrine neoplasia type 1 (14 cases) and with familial adenomatous polyposis (1 case). Only one rogue cell was found among the 15 cells with double minutes.

[In vitro effects of IL-2 on human hypophyseal adenoma]. / Effetti in vitro della IL-2 su adenomi ipofisari umani.

The effects of two different concentrations of IL-2 on human pituitary adenomas (one secreting ACTH and one secreting GH) were evaluated in vitro. A specimen of the tumor was dissagregated and the cells were incubated for three days with RPMI 1640 medium. The medium was then decanted and the cells were incubated with 1 mlo of fresh medium for three hours and then with new fresh medium containing two different concentrations of IL-2, 100U/ml, for three hours too. The pituitary hormones, ACTH and GH, released into the medium were assayed by RIA. Dose of 100 U IL-2 induced a profound increase of ACTH release. The other dose decreased ACTH release. The release of GH was suppressed by IL-2 at the two concentrations tested. IL-2 may be an immunologic messenger exerting direct action at pituitary level. It appears probable that IL-2 plays an important role in determining the response of the pituitary to stress and infections.

Chromosome abnormalities in a case of pituitary adenoma.

Chromosome analysis of primary cultures from an ACTH-secreting pituitary adenoma revealed the presence of one clone of cells with deletion of 18p and some random structural and numerical abnormalities.

[Hashimoto's thyroiditis and HLA in Caucasian Italians]. / Tiroidite di Hashimoto e HLA in caucasici italiani.

Sixty cases of goitrous Hashimoto's thyroiditis were observed at the first diagnosis. For 18 of the cases, the diagnosis was made only on the basis of cytological examination since antithyroid antibodies were always negative. To determine if seronegative or seropositive forms constituted a particular genetically determined subgroup, we evaluated whether such peculiarities were related to specific HLA haplotype. Analysis of HLA antigens showed in the seropositive a significant increase in the frequency of HLA-B51 and HLA-A2, a significant decrease in the frequency of HLA-A1 and HLA-DR1. In seronegative cases no increase was found in the frequency of HLA-A-B-DR antigens, but they showed a strong positive association with HLA-DQ3. Our results show that association of Hashimoto's thyroiditis with HLA antigens was different in seronegative and seropositive subgroup. This finding would seem to support the hypothesis that in a few subjects the entire immune process develops exclusively within the involved organ and this process would be genetically determined.

[Seronegative hashitoxicosis in patient with rheumatoid arthritis]. / Hashitossicosi sieronegativa in paziente con artrite reumatoide.

Hashimoto's thyroiditis is known to occur in conjunction with other autoimmune disorders including rheumatoid arthritis. We describe herein a patient with long before-onset seronegative rheumatoid arthritis who developed Hashimoto's thyroiditis and hyperthyroidism without serologic evidence of thyroglobulin, microsomal and/or anti-TSH receptor antibodies. The occurrence of these autoimmune diseases in individual patients suggests an imbalance in immune function which effects more than one organ system. The predisposition to this spectrum of autoimmune diseases may be genetically determined, with specific HLA haplotypes associated with a variety of autoimmune diseases. The case of this patient provides the demonstration that intrathyroidal lymphocytes in autoimmune thyroid disorders and T-lymphocytes in the synovium are responsible for mediating the glandular destruction in Hashimoto disease and intraarticular lesions in rheumatoid arthritis, since the disorders can exist without evidence of a systemic immune response.

Effects of cimetidine on in vitro transformation of peripheral monocytes to macrophages in healthy volunteers and cancer patients.

Monocyte-to-macrophage transformation is a phenomenon which correlates with the absolute number of mononuclear cells, principally lymphocytes, contained in the culture. The addition of cimetidine to cultures of mononuclear cells from the peripheral blood of healthy volunteers enhances monocyte transformation (probably by way of blocking the H2 receptors of suppressors T lymphocytes) regardless of the absolute number of monocytes in the culture or of basal transformation rates. Removal of the lymphocytes from the cultures lowers the basal transformation rate and prevents the effect of cimetidine. The addition of histamine to the cultures causes significant depression of the monocyte transformation rate; this effect is partly offset by the concurrent addition of cimetidine. In the case of cancer patients, mononuclear cell cultures from peripheral blood fail to respond to cimetidine even though basal transformation rates are not significantly different from those of healthy controls; this suggests some intrinsic impairment of monocyte function, possibly mediated by blocking factors produced by the tumor.

[Protective effect of lithium carbonate in neutropenia induced by antiblastic agents and evaluation of its long-term efficacy]. / Effetto protettivo de litio carbonato nella neutropenia da antiblastici e valutazione della sua efficacia a distanza.

The association of lithium carbonate and antiblastic drugs has been studied in 22 patients suffering from tumours to see whether it was able to prevent or attenuate the neutropenising effect and establish whether its protection action on leucocytaemia was not just transitory but was maintained for prolonged treatment also. Patients were submitted to four oncolytic treatment cycles during which administration with LiCO3 was associated with the first and third cycles (LNLN sequence) in 14 patients and with the second and fourth (NLNL sequence) in the other 8. Statistical analysis of the results obtained confirmed that lithium carbonate performs a protective action with respect to antiblastic-induced neutropenia and that the action is long term. The drop in monocytes also seems to diminish after administration of lithium carbonate.