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Biomedical subjects

G Iodice

Publications and source records attributed to G Iodice.

10 recordsLinked to original sources

Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44.

Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.

Bone Marrow

A disturbance of the IL-2/IL-2 receptor system parallels the activity of multiple myeloma.

The IL-2/IL-2 receptor (IL-2R) system has been investigated in 64 patients with multiple myeloma (MM), 31 with monoclonal gammopathies of undetermined significance (MGUS) and 20 normal controls. The MM data were related to clinical status by comparing active disease, i.e. at diagnosis and at relapse, and stable disease, i.e. complete remission and off-treatment plateau phase. Serum and urinary values of the soluble IL-2R (sIL-2R) were significantly increased in MM patients compared with normal controls and this increase was related to activity. MM patients with active disease gave significantly higher values than those with stable disease. Compared with normal controls, enriched B cell (but not T cell) preparations from peripheral blood mononuclear cells (PBMC) showed significantly increased proportions of IL-2R+ cells in MM and MGUS. However, the highest proportions were detected in active MM compared with stable MM and MGUS. Also, 16% of all MM patients, as opposed to 9% of MGUS, had well-defined bone marrow IL-2R+ plasma cell populations. The lowest serum IL-2 values were found in active MM. Serial follow up of serum sIL-2R suggested that this peptide can be used as an additional marker of active malignancy. The data indicate that a disturbance of IL-2/IL-2R system is most pronounced in active MM. These findings may provide clues as to the T cell abnormalities in MM.

Aged

Treatment of adult patients with idiopathic thrombocytopenic purpura with intravenous immunoglobulin: effects on circulating T cell subsets and PWM-induced antibody synthesis in vitro.

Eight adult patients with idiopathic thrombocytopenic purpura (ITP) were given two 5-d courses of intermediate (250 mg/kg body weight/d) to high dose (400 mg/kg body weight/d) intravenous infusions of human plasmin-cleaved Ig, at 15-30 d intervals. Three patients also were given single booster infusions (400 mg/kg body weight for 1 d) of a different preparation, S-sulfonated Ig. As expected, significant though transient rises in the platelet count were consistently observed in all patients. The mean platelet count increase was 95 600/mm3 after the first course, and 143 500/mm3 after the second course. Similar effects of lower magnitude were obtained several times in the patients given single booster doses. In three patients, platelet-bound IgG levels were decreased in association with Ig therapy. Phenotypic analysis of T cell subsets before starting Ig therapy and at the end of the second high dose course of intravenous Ig treatment revealed significant reductions in the proportion of T4+ lymphocytes in five patients and relative increases in the percentage of T8+ cells after therapy. As the overall proportion of T3+ cells remained unchanged, the T4+/T8+ ratio was therefore decreased. The total number of circulating lymphocytes was also decreased following therapy. In addition, PWM-driven Ig biosynthesis in vitro was significantly impaired after therapy in most patients, the capacity to synthesize IgG being mainly affected. It is concluded that, in addition to the reported transient blockade of the reticuloendothelial system, non-specific suppression of polyclonal Ig biosynthesis induced by the high dose Ig infusions also contributes to the net increase in platelet count.

Adolescent

Cyclic lysozyme administration as a tool for immunopotentiation in patients with multiple myeloma.

Fourteen patients with multiple myeloma (MM) were given chemotherapy courses for 7 days followed by 21-day intervals, combined with an immunomodulating treatment, namely lysozyme (LZM), 2 g daily for three weeks every other interval. Some parameters of cell-mediated immunity (total-E-rosettes, monocyte and polymorphonuclear leukocyte chemotaxis, skin tests) as well as humoral immunity (serum Ig levels, electrophoresis, immunoelectrophoresis) were evaluated comparatively in the intervals with and in those without LZM administration. A significant increase in total-E-rosettes and monocyte chemotaxis was observed in about half of the patients studied, this enhancement being accompanied by a reduction in both frequency and severity of viral and bacterial infections. No side-effects ascribable to LZM were recorded in any of the patients.

Adjuvants, Immunologic

[Immunological deficiency syndromes, immunosuppression by drugs and occurrence of neoplasms: a casual association?].

Although supported by a number of experimental models, the assumption assigning a crucial role to the immune system in the antineoplastic defense mechanisms has not been convincingly demonstrated so far for human tumors. Should the theory be correct, severe functional impairment of the immune system would obviously result in the occurrence of tumors with abnormally high frequency. Registry holdings systematically collecting pertinent information on the malignancies developed in patients with primary immunodeficiency diseases or in organ transplant recipients maintained on therapeutically-induced immune depression, as well as the observation of tumors occurring in patients treated with immunosuppressive agents and of second malignancies arising after radio- and/or chemotherapy of the primary tumor consistently indicate that depressed immunity is usually associated with an increased incidence of cancer as compared with that expected in the general control populations. However, not all types of tumors are increased to the same extent, in that lymphoreticular neoplasias (especially non-Hodgkin's lymphomas), acute leukemias as second tumors and, among solid neoplasms, squamous cell carcinomas are those most frequently reported. These observations suggest that even deeply impaired tumoricidal immune mechanisms may facilitate the growth of certain tumors only, especially of those arising from the cells of the immune system itself, in remarkable contrast with their frequency in the general population. Oncogenesis may be favoured in various states of depressed immunity by a number of ways. Their elucidation might have bearing on the comprehension of the more general phenomenon of the neoplastic transformation.

Carcinoma, Squamous Cell

Arginine thiazolidinecarboxylate in the treatment of chronic active hepatitis: double-blind comparison with placebo.

Forty-four patients with chronic active hepatitis were given arginine thiazolidinecarboxylate (800 mg/day per os for 40 days) or placebo in a randomized, double-blind trial. The most important liver function parameters were measured in each patient at the beginning of the trial, after 20 days, and at the end of the trial. The active drug lessened the parameters of necrosis and cholestasis while protein synthesis improved in liver cells. The differences between ATCA and placebo groups were highly significant. No treatment-related side-effects were reported.

Adolescent

Prophylactic sclerotherapy of high-risk esophageal varices: results of a multicentric prospective controlled trial.

In this prospective, multicenter trial, 140 cirrhotic patients with no previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage were randomized to receive either sclerotherapy or conservative treatment for the prevention of first variceal bleeding. The end-points of the study were bleeding and death. Life table curves showed that prophylactic sclerotherapy significantly diminished the incidence of variceal hemorrhage (p less than 0.001) and overall mortality (p less than 0.01). Two-year cumulative bleeding rate was 18% in the sclerosis group (95% confidence interval = 10 and 31) and 57% (95% confidence interval = 40 and 72) in the control group. Two-year cumulative mortality rate was 30% (95% confidence interval = 19 and 45) in the sclerotherapy group and 56% (95% confidence interval = 39 and 72) in the controls. One patient died after hemorrhage from an ulcer secondary to sclerotherapy. Analysis by the Cox model of the factors potentially confounding or interacting with the effect of sclerotherapy suggested that sclerotherapy was more efficient in preventing first bleeding in patients with decompensated disease (Child B and C) than in those in good condition (Child A). However, the 2-year cumulative bleeding rate of untreated Child A patients was only 19%, showing how in this group the endoscopic findings were unreliable in selecting high-risk varices and explaining why after a 2-year follow-up prophylactic sclerosis did not show any benefit in such patients. We conclude that sclerotherapy can decrease the incidence of first variceal bleeding and death for a period of 2 years in cirrhotic patients with high-risk varices.

Adult

Analogues in immunology.

A number of immunological functions has been found to be endowed with biological rhythmicity. Variations of peripheral blood lymphocytes, immediate and delayed hypersensitivity responses, and reactivity of the immune system to antigenic challenge have consistently shown circadian bioperiodicity. By employing a panel of monoclonal antibodies specific for the various lymphocyte subsets, we have been able to detect rhythmic variations in the number of total T lymphocytes, as well as of the T helper (TH) and the T suppressor/cytotoxic (Ts) subsets. Available evidence clearly indicates such circadian variations to be due to compartmentalization of circulating lymphocytes in several lymphoid organs. Biological rhythms (circadian, circaseptan, etc.) have been demonstrated in several immunological situations of clinical interest, including variations of TH and Ts cells in patients with rheumatoid arthritis incidence of allograft rejections, antitumoral effectiveness of chemoimmunotherapy, and allergic symptoms. In addition, the recent availability of synthetic analogues of some thymic peptide hormones and of the synthetic ACTH 1-17 (Synchrodyn 1-17 is greatly contributing to the elucidation of the role of such hormones in the immune regulation process. A preliminary account is reported of the experiments performed with the aim of raising conventional rabbit antisera to the peptide analogue ACTH 1-17, as well as of the consistently negative results which were obtained when 578 human serum samples (from patients treated with such synthetic peptide) were screened by a radioimmunoassay for the occurrence of anti-ACTH 1-17 antibodies. It is emphasized that the recognition of the rhythmic variations of several immunological mechanisms and of the crucial role played by the analogues of adrenal corticotropic and thymic hormones in immune regulation has favoured significant advances in the fast growing area of chronoimmunology.

Adrenocorticotropic Hormone

[Idiopathic CD4+ lymphocytopenia: a case report].

We present the case of a 47-year-old patient who was seen for recurrent opportunistic infections. Immunophenotypic analyses disclosed severe reduction of CD4+ T cells. Repeated Elisa, Western blot and polymerase chain reaction tests for HIV were negative. The low CD4+ T lymphocyte count unaccompanied by increased CD8+ T lymphocytes and hypergammaglobulinemia, along with negativity for HIV infection, suggested the diagnosis of idiopathic CD4+ lymphocytopenia (ICL). The patient's clinical manifestations and laboratory results conformed with the case definition of ICL established in 1992 by the Centers for Disease Control of Atlanta, i.e., CD4+ T cells < 300/mm3 on two occasions and no evidence of HIV infection. In vitro analyses evidenced depressed lymphoproliferative responses to mitogens such as concanavalin A and pokeweed mitogen, while the expression of Fas antigen on peripheral lymphocytes and the percentage of apoptotic cells after propidium iodide staining were increased. Since in vitro concanavalin A stimulation inhibits T cell proliferation and induces apoptosis, these results suggest that the patient's lymphocytes are susceptible, in vivo, to an apoptotic signal.

Apoptosis