[Interferon as a sensitizing agent toward chemotherapy in a case of multiple myeloma refractory to treatment].
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Biomedical subjects
Publications and source records attributed to L Bonomo.
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We have examined the distribution of B and T lymphocytes, T-cells with helper/inducer (T4+) or suppressor/cytotoxic (T8+) phenotypes and a subset of cells with natural killer (NK) activity and positive for the Leu 7 (HNK-1) surface antigen in peripheral blood and in lymphocyte-rich pleural effusions of patients with tuberculosis or malignancies (mesothelioma and lung cancer with pleural metastasis). In individual patients, the percentages of T lymphocytes were uniformly higher in pleural effusions than in peripheral blood; however, lower percentages of B lymphocytes and cells positive for the Leu 7 antigen were present in pleural fluids. The analysis of T-cell subpopulations demonstrated a selective enrichment of T lymphocytes with helper/inducer phenotype in pleural effusions, while the percentages of T-cells with suppressor/cytotoxic phenotype were similar in pleural fluid and peripheral blood. These results indicate that in lymphocytic pleural effusions the main lymphoid cell population is represented by T lymphocytes with helper/inducer phenotype, regardless of whether the effusion is due to tuberculosis or malignancies such as mesothelioma or lung cancer.
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Plasma lipoproteins inhibit immune function. Polymorphonuclear cell (PMN) and monocyte activities, and pokeweed mitogen (PWM)-driven B cell differentiation in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia were evaluated. Evidence is provided for a selective impairment of these functional capacities in type IIa and type IIb hyperlipoproteinaemic patients, while immune responsiveness is unaffected in type IV primary hyperlipoproteinaemia. The data suggest a specific immune dysfunction in patients with type IIa and type IIb primary hyperlipoproteinaemia.
Over the last four years the authors performed transcatheter embolization of the splenic artery by Gianturco coils in 32 consecutive cirrhotic patients with portal hypertension, splenomegaly, cytopenia and gastro-esophageal varices endoscopically proved. This procedure was especially useful for treatment of splenomegaly and cytopenia because a constant reduction of spleen dimensions and increase in platelet count were registered. The effectiveness of transcatheter embolization and follow-up are based on clinic, hematologic and sonographic findings. We believe sonographic monitoring to be very useful both to evaluate splenomegaly and signs of portal hypertension and to reveal splenic complications (abscesses). We never registered severe complications.
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Seven patients with type II idiopathic mixed cryoglobulinemia were treated with recombinant human leukocyte interferon (alpha interferon). In all of them, a conspicuous reduction of circulating cryoglobulins was noted, together with a definite, remarkable improvement of the clinical pattern. The immunologic parameters (natural killer cell activity and phagocytosis, among others) improved as well; side effects were usually mild and transient. Increases in the cryoglobulin level occurred in a few cases, but they were at least partly sensitive to readministration of alpha interferon treatment. The favorable results obtained in these cases of idiopathic cryoglobulinemia seem to be consistent and prolonged.
The B cell responsiveness mediated by T cells has been evaluated in 50 aged donors by using a Pokeweed mitogen (PWM)-driven differentiation system. Peripheral blood mononuclear cells (PBMC) from aged donors exhibited a lower plaque-forming cell (PFC) generation in comparison with young donors. Similar results were obtained by using, on a per cell basis, purified T cells supplemented with Non-T lymphocytes. OKT4+ cell addition to Non-T cells enhanced PFC number, even if values were still lower when compared to young donors. Moreover, results similar to those seen with T-supplemented Non-T cell cultures were obtained by mixing Non-T cells with OKT4+ and OKT8+ lymphocytes. Interestingly, when OKT8+ cells were divided into OKT8+M1+ and OKT8+M1-subsets and used in the assay, both cell fractions suppressed B cell response in aged donors, while this effect was mediated by OKT8+M1+ cells only in the young counterpart. Soluble suppressive factors were responsible for the observed activity, since indomethacin supplementation to cultures or overnight incubation of cells before PWM stimulation abrogated the OKT8+M1--mediated suppression. Taken together, these findings suggest an additional alteration of T-B cell relationship in the elderly.
Senescence of the immune system leads to a decline of functional capacities of lymphoid cells. In this regard, evidence has been provided for a reduction of T and B cell-mediated responses. T-B regulation is also affected by the aging process. Since the proportion of lymphocytes is similar to that observed in young donors, either intracellular or extracellular factors may play an important role in the impaired immunoresponsiveness. An intrinsic defect of T or B cells has been in fact postulated. However, soluble suppressive factors or decreased LK production seem to represent the key events involved in the decline of the immune response. Nevertheless, over the past few years emphasis has been given to the increased lymphocyte membrane microviscosity in the elderly [Rivnay et al: Mech Ageing Dev 10: 71-79, 1979]. All together, these findings suggest a multifactorial therapeutic approach for the correction of the impaired immune response in aged individuals.
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The case of a patient with B cell chronic lymphocytic leukemia (CLL) and T-lymphocyte-rich pleural effusion secondary to carcinoma of the lung is presented. Monoclonal B cells were the main cell population in the peripheral blood and the helper/suppressor cell ratio of the residual T lymphocytes was lower than 1. On the contrary, T lymphocytes with helper phenotype were prevalent in the pleural fluid. The results indicate that local factors influence strongly the distribution of the lymphocyte subpopulations in different districts of the body and suggest that an etiopathogenesis unrelated to the B cell lymphoproliferative disease must be searched for, when a T-cell-rich pleural effusion is present.
We present a patient with multiple myeloma and double (IgA kappa + IgG kappa) paraproteinaemia in the serum. Immunofluorescence analysis of bone marrow plasma cell with fluorochrome-conjugated goat antibodies specific for mu, delta, gamma or alpha immunoglobulin heavy chain and kappa or lambda light chains revealed the presence of a plasma cell clone synthesizing simultaneously gamma, alpha and kappa chains. A minority of plasma cells synthesized gamma or alpha chains separately. Moreover, in the patient's peripheral blood, a few cells with the morphology of lymphoplasmoblasts and simultaneously positive for gamma, alpha and kappa chains were also detected. These results indicate that in this patient, the neoplastic plasma cell clone was 'frozen' at the differentiative step of the switch from IgG to IgA synthesis.
Percutaneous occlusion of the spermatic vein has been performed in 104 patients with varicocele in the last five years. We report our long-term results on the first 87 cases with a follow-up of at least six months. The occlusion of the gonadal vein is generally induced by selective transcatheter injection of sclerosing agent. Our patients are always evaluated before and after sclerotherapy by telethermography and/or doppler examination. Furthermore spermiogram is obtained before and six months after therapy. We registered only four recurrences with no major complications.
T helper (Th) and T suppressor (Ts) functions on the induction of specific antibody response have been studied in 80 aged individuals by means of a plaque-forming cell assay. Of the subjects 45.2% exhibited a reduction of Ts activity on Ig production by adding Concanavalin A (Con A) to cultures on day 0, while 35.7% of aged donors showed a decrease of Th functions by supplementation of Con A on day 2. A small number of individuals displayed a combined deficit (Th + Ts). Furthermore, these defects seem to be related to soluble suppressive factors which might adhere to cell surface. In fact, preincubation of peripheral blood mononuclear cells (PBMC) before their addition to cultures and resuspension in fresh medium normalized the immunoregulatory defects. On the other hand, overnight supernatants from old PBMC transferred to young PBMC cultures induced the same deficit observed in the aged cell suspensions. Finally, Zinc chloride supplementation to cultures was able to correct the deficient Th activity only. These data suggest an additional defect of immunoregulation in the elderly.
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